. 2015 Nov; 9(10):1936-65.
doi: 10.1016/j.molonc.2015.10.008.

Negative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy

Anna Śledzińska 1 Laurie Menger 1 Katharina Bergerhoff 1 Karl S Peggs 2 Sergio A Quezada 3 
  • PMID: 26578451
  •     351 References
  •     33 citations


The term 'inhibitory checkpoint' refers to the broad spectrum of co-receptors expressed by T cells that negatively regulate T cell activation thus playing a crucial role in maintaining peripheral self-tolerance. Co-inhibitory receptor ligands are highly expressed by a variety of malignancies allowing evasion of anti-tumour immunity. Recent studies demonstrate that manipulation of these co-inhibitory pathways can remove the immunological brakes that impede endogenous immune responses against tumours. Antibodies that block the interactions between co-inhibitory receptors and their ligands have delivered very promising clinical responses, as has been shown by recent successful trials targeting the CTLA-4 and PD-1 pathways. In this review, we discuss the mechanisms of action and expression pattern of co-inhibitory receptors on different T cells subsets, emphasising differences between CD4(+) and CD8(+) T cells. We also summarise recent clinical findings utilising immune checkpoint blockade.

Keywords: CTLA-4; Cancer immunotherapy; Inhibitory checkpoints; Inhibitory receptors on T cells; PD-1.

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Caroline Robert, Georgina V Long, +25 authors, Paolo A Ascierto.
N Engl J Med, 2014 Nov 18; 372(4). PMID: 25399552
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CTLA-4 can function as a negative regulator of T cell activation.
T L Walunas, D J Lenschow, +5 authors, J A Bluestone.
Immunity, 1994 Aug 01; 1(5). PMID: 7882171
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The cell-cell adhesion molecule carcinoembryonic antigen-related cellular adhesion molecule 1 inhibits IL-2 production and proliferation in human T cells by association with Src homology protein-1 and down-regulates IL-2 receptor.
Charng-Jui Chen, John E Shively.
J Immunol, 2004 Mar 09; 172(6). PMID: 15004155
Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1.
Gang Xiao, Anqi Deng, +2 authors, Xiaolong Liu.
Proc Natl Acad Sci U S A, 2012 Sep 06; 109(38). PMID: 22949674    Free PMC article.
Dysregulated expression of CD66a (BGP, C-CAM), an adhesion molecule of the CEA family, in endometrial cancer.
A M Bamberger, L Riethdorf, +7 authors, T Löning.
Am J Pathol, 1998 Jun 17; 152(6). PMID: 9626043    Free PMC article.
The carboxyl-terminal region of biliary glycoprotein controls its tyrosine phosphorylation and association with protein-tyrosine phosphatases SHP-1 and SHP-2 in epithelial cells.
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J Biol Chem, 1998 Dec 29; 274(1). PMID: 9867848
Structure of murine CTLA-4 and its role in modulating T cell responsiveness.
D A Ostrov, W Shi, +2 authors, S G Nathenson.
Science, 2000 Oct 29; 290(5492). PMID: 11052947
A soluble lymphocyte activation gene-3 (sLAG-3) protein as a prognostic factor in human breast cancer expressing estrogen or progesterone receptors.
Frédéric Triebel, Kamel Hacene, Marie-France Pichon.
Cancer Lett, 2005 Jun 11; 235(1). PMID: 15946792
TIGIT and PD-1 impair tumor antigen-specific CD8⁺ T cells in melanoma patients.
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J Clin Invest, 2015 Apr 14; 125(5). PMID: 25866972    Free PMC article.
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The TIM gene family regulates autoimmune and allergic diseases.
Jennifer Hartt Meyers, Catherine A Sabatos, Sumone Chakravarti, Vijay K Kuchroo.
Trends Mol Med, 2005 Jul 09; 11(8). PMID: 16002337
Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR.
Noa Stanietsky, Tihana Lenac Rovis, +6 authors, Ofer Mandelboim.
Eur J Immunol, 2013 May 17; 43(8). PMID: 23677581    Free PMC article.
Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains.
P Dariavach, M G Mattéi, P Golstein, M P Lefranc.
Eur J Immunol, 1988 Dec 01; 18(12). PMID: 3220103
CD4⁺ follicular helper T cell infiltration predicts breast cancer survival.
Chunyan Gu-Trantien, Sherene Loi, +21 authors, Karen Willard-Gallo.
J Clin Invest, 2013 Jun 20; 123(7). PMID: 23778140    Free PMC article.
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Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death.
Y Ishida, Y Agata, K Shibahara, T Honjo.
EMBO J, 1992 Nov 01; 11(11). PMID: 1396582    Free PMC article.
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Comprehensive molecular portraits of human breast tumours.
Cancer Genome Atlas Network.
Nature, 2012 Sep 25; 490(7418). PMID: 23000897    Free PMC article.
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IL-18 induces PD-1-dependent immunosuppression in cancer.
Magali Terme, Evelyn Ullrich, +14 authors, Laurence Zitvogel.
Cancer Res, 2011 Jul 05; 71(16). PMID: 21724589
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Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1.
S A Marsters, T M Ayres, +3 authors, A Ashkenazi.
J Biol Chem, 1997 May 30; 272(22). PMID: 9162022
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Immune modulation by melanoma and ovarian tumor cells through expression of the immunosuppressive molecule CD200.
A Siva, H Xin, +3 authors, A Kretz-Rommel.
Cancer Immunol Immunother, 2007 Dec 07; 57(7). PMID: 18060403
TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation.
Jennifer Hartt Meyers, Sumone Chakravarti, +9 authors, Vijay K Kuchroo.
Nat Immunol, 2005 Mar 29; 6(5). PMID: 15793576
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Novel immunotherapy for malignant melanoma with a monoclonal antibody that blocks CEACAM1 homophilic interactions.
Rona Ortenberg, Yair Sapir, +10 authors, Gal Markel.
Mol Cancer Ther, 2012 Apr 03; 11(6). PMID: 22466331
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Blood, 1997 Aug 15; 90(4). PMID: 9269779
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The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells.
Xin Yu, Kristin Harden, +9 authors, Jane L Grogan.
Nat Immunol, 2008 Nov 18; 10(1). PMID: 19011627
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Induction of the CTLA-4 gene in human lymphocytes is dependent on NFAT binding the proximal promoter.
Heather M Gibson, Carrie J Hedgcock, +4 authors, Henry K Wong.
J Immunol, 2007 Sep 06; 179(6). PMID: 17785820    Free PMC article.
Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.
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J Clin Oncol, 2014 Mar 05; 32(10). PMID: 24590637    Free PMC article.
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Breast cancer cell CD200 expression regulates immune response to EMT6 tumor cells in mice.
Reginald M Gorczynski, Zhiqi Chen, +4 authors, Julia Behnke.
Breast Cancer Res Treat, 2009 Dec 03; 123(2). PMID: 19953316
CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent.
Luca Gattinoni, Anju Ranganathan, +6 authors, Nicholas P Restifo.
Blood, 2006 Aug 03; 108(12). PMID: 16882704    Free PMC article.
Biliary glycoprotein (CD66a), a cell adhesion molecule of the immunoglobulin superfamily, on human lymphocytes: structure, expression and involvement in T cell activation.
R Kammerer, S Hahn, +2 authors, S von Kleist.
Eur J Immunol, 1998 Dec 08; 28(11). PMID: 9842909
Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses.
Nicole Joller, Ester Lozano, +13 authors, Vijay K Kuchroo.
Immunity, 2014 Apr 22; 40(4). PMID: 24745333    Free PMC article.
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Cutting edge: CTLA-4 on effector T cells inhibits in trans.
Emily Corse, James P Allison.
J Immunol, 2012 Jul 04; 189(3). PMID: 22753941
Genome-wide DNA methylation analysis identifies hypomethylated genes regulated by FOXP3 in human regulatory T cells.
Yuxia Zhang, Jovana Maksimovic, +5 authors, Leonard C Harrison.
Blood, 2013 Aug 27; 122(16). PMID: 23974203    Free PMC article.
Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function.
G J Wright, M J Puklavec, +4 authors, A N Barclay.
Immunity, 2000 Sep 12; 13(2). PMID: 10981966
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VISTA is an immune checkpoint molecule for human T cells.
J Louise Lines, Eirini Pantazi, +8 authors, Randolph Noelle.
Cancer Res, 2014 Apr 03; 74(7). PMID: 24691993    Free PMC article.
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CD200 is induced by ERK and is a potential therapeutic target in melanoma.
Kimberly B Petermann, Gabriela I Rozenberg, +10 authors, Norman E Sharpless.
J Clin Invest, 2007 Nov 17; 117(12). PMID: 18008004    Free PMC article.
Molecular definition of a novel human galectin which is immunogenic in patients with Hodgkin's disease.
O Türeci, H Schmitt, +2 authors, U Sahin.
J Biol Chem, 1997 Mar 07; 272(10). PMID: 9045665
Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients.
F Stephen Hodi, Martin C Mihm, +14 authors, Glenn Dranoff.
Proc Natl Acad Sci U S A, 2003 Apr 17; 100(8). PMID: 12682289    Free PMC article.
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Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor.
H Nishimura, M Nose, +2 authors, T Honjo.
Immunity, 1999 Sep 15; 11(2). PMID: 10485649
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FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy.
Hazem Ghebeh, Eman Barhoush, +3 authors, Said Dermime.
BMC Cancer, 2008 Feb 26; 8. PMID: 18294387    Free PMC article.
C-CAM1, a candidate tumor suppressor gene, is abnormally expressed in primary lung cancers.
L Wang, S H Lin, +4 authors, L Mao.
Clin Cancer Res, 2000 Aug 24; 6(8). PMID: 10955775
Covalent dimerization of CD28/CTLA-4 and oligomerization of CD80/CD86 regulate T cell costimulatory interactions.
J L Greene, G M Leytze, +4 authors, P S Linsley.
J Biol Chem, 1996 Oct 25; 271(43). PMID: 8900156
Exhaustion of tumor-specific CD8⁺ T cells in metastases from melanoma patients.
Lukas Baitsch, Petra Baumgaertner, +9 authors, Daniel E Speiser.
J Clin Invest, 2011 May 11; 121(6). PMID: 21555851    Free PMC article.
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Reviving exhausted T lymphocytes during chronic virus infection by B7-H1 blockade.
Sheng Yao, Lieping Chen.
Trends Mol Med, 2006 May 03; 12(6). PMID: 16650803
Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice.
Taku Okazaki, Yoshimasa Tanaka, +8 authors, Tasuku Honjo.
Nat Med, 2003 Nov 05; 9(12). PMID: 14595408
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Cutting edge: A monoclonal antibody specific for the programmed death-1 homolog prevents graft-versus-host disease in mouse models.
Dallas B Flies, Shengdian Wang, Haiying Xu, Lieping Chen.
J Immunol, 2011 Jul 20; 187(4). PMID: 21768399    Free PMC article.
VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses.
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J Exp Med, 2011 Mar 09; 208(3). PMID: 21383057    Free PMC article.
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Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity.
Tyler J Curiel, Shuang Wei, +19 authors, Weiping Zou.
Nat Med, 2003 Apr 22; 9(5). PMID: 12704383
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Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice.
Sheng Xiao, Craig R Brooks, +9 authors, Vijay K Kuchroo.
Proc Natl Acad Sci U S A, 2012 Jul 10; 109(30). PMID: 22773818    Free PMC article.
Inhibitory B7-family molecules in the tumour microenvironment.
Weiping Zou, Lieping Chen.
Nat Rev Immunol, 2008 May 27; 8(6). PMID: 18500231
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Sequence, structure, function, immunity: structural genomics of costimulation.
Kausik Chattopadhyay, Eszter Lazar-Molnar, +7 authors, Steven C Almo.
Immunol Rev, 2009 May 12; 229(1). PMID: 19426233    Free PMC article.
CTLA-4 control over Foxp3+ regulatory T cell function.
Kajsa Wing, Yasushi Onishi, +5 authors, Shimon Sakaguchi.
Science, 2008 Oct 11; 322(5899). PMID: 18845758
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Structural and functional analysis of the costimulatory receptor programmed death-1.
Xuewu Zhang, Jean-Claude D Schwartz, +9 authors, Steven C Almo.
Immunity, 2004 Mar 20; 20(3). PMID: 15030777
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Bimodal regulation of T cell-mediated immune responses by TIM-4.
Masayuki Mizui, Takashi Shikina, +5 authors, Hitoshi Kikutani.
Int Immunol, 2008 Mar 28; 20(5). PMID: 18367551
The expression of mouse biliary glycoprotein, a carcinoembryonic antigen-related gene, is down-regulated in malignant mouse tissues.
M Rosenberg, P Nédellec, +3 authors, N Beauchemin.
Cancer Res, 1993 Oct 15; 53(20). PMID: 8402684
Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function.
K S Hathcock, G Laszlo, +2 authors, R J Hodes.
J Exp Med, 1994 Aug 01; 180(2). PMID: 7519245    Free PMC article.
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BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1.
Norihiko Watanabe, Maya Gavrieli, +11 authors, Kenneth M Murphy.
Nat Immunol, 2003 Jun 11; 4(7). PMID: 12796776
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Secondary but not primary T cell responses are enhanced in CTLA-4-deficient CD8+ T cells.
C A Chambers, T J Sullivan, T Truong, J P Allison.
Eur J Immunol, 1998 Nov 10; 28(10). PMID: 9808182
The role of NK cell recognition of nectin and nectin-like proteins in tumor immunosurveillance.
Anja Fuchs, Marco Colonna.
Semin Cancer Biol, 2006 Aug 15; 16(5). PMID: 16904340
Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial.
Kim Margolin, Marc S Ernstoff, +12 authors, F Stephen Hodi.
Lancet Oncol, 2012 Mar 30; 13(5). PMID: 22456429
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LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems.
Joseph F Grosso, Cristin C Kelleher, +10 authors, Charles G Drake.
J Clin Invest, 2007 Oct 13; 117(11). PMID: 17932562    Free PMC article.
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Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study.
Ajay V Maker, Giao Q Phan, +11 authors, Steven A Rosenberg.
Ann Surg Oncol, 2005 Nov 12; 12(12). PMID: 16283570    Free PMC article.
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Differential expression of CD66a (BGP), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland.
L Riethdorf, B W Lisboa, +3 authors, T Löning.
J Histochem Cytochem, 1997 Jul 01; 45(7). PMID: 9212821
PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine.
T Okazaki, A Maeda, +2 authors, T Honjo.
Proc Natl Acad Sci U S A, 2001 Nov 08; 98(24). PMID: 11698646    Free PMC article.
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PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma.
Ryo Yamamoto, Momoko Nishikori, +8 authors, Takashi Uchiyama.
Blood, 2008 Jan 22; 111(6). PMID: 18203952
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The mouse homologue of the leukocyte-associated Ig-like receptor-1 is an inhibitory receptor that recruits Src homology region 2-containing protein tyrosine phosphatase (SHP)-2, but not SHP-1.
Robert Jan Lebbink, Talitha de Ruiter, +2 authors, Linde Meyaard.
J Immunol, 2004 Apr 22; 172(9). PMID: 15100296
The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity.
Noa Stanietsky, Hrvoje Simic, +11 authors, Ofer Mandelboim.
Proc Natl Acad Sci U S A, 2009 Oct 10; 106(42). PMID: 19815499    Free PMC article.
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Clinical impact of herpesvirus entry mediator expression in human hepatocellular carcinoma.
Daisuke Hokuto, Masayuki Sho, +4 authors, Yoshiyuki Nakajima.
Eur J Cancer, 2014 Dec 04; 51(2). PMID: 25468715
A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC.
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Eur J Immunol, 2009 Feb 07; 39(3). PMID: 19197944    Free PMC article.
Paclitaxel, topotecan and rituximab: long term outcomes of an effective salvage programme for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.
Jason R Westin, Peter McLaughlin, +13 authors, Anas Younes.
Br J Haematol, 2014 Jul 22; 167(2). PMID: 25039868    Free PMC article.
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Genomics, 1999 Sep 24; 60(3). PMID: 10493833
B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance.
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Blood, 2010 May 18; 116(8). PMID: 20472828    Free PMC article.
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Expression of biliary glycoprotein (CD66a) in normal and malignant breast epithelial cells.
J Huang, J F Simpson, +3 authors, J E Shively.
Anticancer Res, 1998 Dec 22; 18(5A). PMID: 9858884
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Patricia A Taylor, Christopher J Lees, +3 authors, Bruce R Blazar.
J Immunol, 2003 Dec 23; 172(1). PMID: 14688306
Clinical significance of CD155 expression in human pancreatic cancer.
Satoshi Nishiwada, Masayuki Sho, +7 authors, Yoshiyuki Nakajima.
Anticancer Res, 2015 Apr 12; 35(4). PMID: 25862891
Expression of nectin 3: Novel prognostic marker of lung adenocarcinoma.
Yoshimasa Maniwa, Wataru Nishio, Yutaka Okita, Masahiro Yoshimura.
Thorac Cancer, 2012 May 01; 3(2). PMID: 28920296
The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity.
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Nat Immunol, 2005 Nov 16; 6(12). PMID: 16286920
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B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells.
Takeshi Azuma, Sheng Yao, +3 authors, Lieping Chen.
Blood, 2008 Jan 29; 111(7). PMID: 18223165    Free PMC article.
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Redefined nomenclature for members of the carcinoembryonic antigen family.
N Beauchemin, P Draber, +22 authors, W Zimmermann.
Exp Cell Res, 2001 Aug 15; 252(2). PMID: 11501563
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Molecular signature of CD8+ T cell exhaustion during chronic viral infection.
E John Wherry, Sang-Jun Ha, +7 authors, Rafi Ahmed.
Immunity, 2007 Oct 24; 27(4). PMID: 17950003
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Carcinoembryonic antigen-related cellular adhesion molecule 1 isoforms alternatively inhibit and costimulate human T cell function.
Daohong Chen, Hideki Iijima, +7 authors, Richard S Blumberg.
J Immunol, 2004 Mar 09; 172(6). PMID: 15004154
Regulation of human intestinal intraepithelial lymphocyte cytolytic function by biliary glycoprotein (CD66a).
V M Morales, A Christ, +11 authors, R S Blumberg.
J Immunol, 1999 Jul 22; 163(3). PMID: 10415036
Antigen-independent induction of Tim-3 expression on human T cells by the common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 is associated with proliferation and is dependent on the phosphoinositide 3-kinase pathway.
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J Immunol, 2012 Mar 17; 188(8). PMID: 22422881
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Mol Immunol, 2011 Oct 18; 49(1-2). PMID: 22000002
Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients.
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J Exp Med, 2010 Sep 08; 207(10). PMID: 20819923    Free PMC article.
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The expression of the Nectin complex in human breast cancer and the role of Nectin-3 in the control of tight junctions during metastasis.
Tracey A Martin, Jane Lane, Gregory M Harrison, Wen G Jiang.
PLoS One, 2014 Jan 05; 8(12). PMID: 24386110    Free PMC article.
Identification and characterization of a transmembrane isoform of CD160 (CD160-TM), a unique activating receptor selectively expressed upon human NK cell activation.
Jérôme Giustiniani, Armand Bensussan, Anne Marie-Cardine.
J Immunol, 2008 Dec 26; 182(1). PMID: 19109136    Free PMC article.
CD160 is essential for NK-mediated IFN-γ production.
Tony C Tu, Nicholas K Brown, +7 authors, Yang-Xin Fu.
J Exp Med, 2015 Feb 26; 212(3). PMID: 25711213    Free PMC article.
The leukocyte/neuron cell surface antigen OX2 binds to a ligand on macrophages.
S Preston, G J Wright, +2 authors, M H Brown.
Eur J Immunol, 1997 Aug 01; 27(8). PMID: 9295026
Galectin-9 regulates T helper cell function independently of Tim-3.
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Glycobiology, 2010 Dec 29; 21(10). PMID: 21187321    Free PMC article.
Enhancement of tumor-reactive cytotoxic CD4+ T cell responses after ipilimumab treatment in four advanced melanoma patients.
Shigehisa Kitano, Takemasa Tsuji, +7 authors, Jedd D Wolchok.
Cancer Immunol Res, 2014 Jan 08; 1(4). PMID: 24396833    Free PMC article.
First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity.
Chrystelle Brignone, Maya Gutierrez, +9 authors, Frédéric Triebel.
J Transl Med, 2010 Jul 27; 8. PMID: 20653948    Free PMC article.
The three HveA receptor ligands, gD, LT-alpha and LIGHT bind to distinct sites on HveA.
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Mol Immunol, 2001 Feb 13; 37(11). PMID: 11164894
Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses.
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Immunity, 2007 Jul 17; 27(1). PMID: 17629517    Free PMC article.
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The costimulatory role of TIM molecules.
Roselynn Rodriguez-Manzanet, Rosemarie DeKruyff, Vijay K Kuchroo, Dale T Umetsu.
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The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice.
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Biliary glycoprotein, a potential human cell adhesion molecule, is down-regulated in colorectal carcinomas.
M Neumaier, S Paululat, +2 authors, C Wagener.
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Crystal structure of murine sCEACAM1a[1,4]: a coronavirus receptor in the CEA family.
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Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction.
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Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family.
R I Montgomery, M S Warner, B J Lum, P G Spear.
Cell, 1996 Nov 01; 87(3). PMID: 8898196
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A2A adenosine receptor protects tumors from antitumor T cells.
Akio Ohta, Elieser Gorelik, +12 authors, Michail Sitkovsky.
Proc Natl Acad Sci U S A, 2006 Aug 19; 103(35). PMID: 16916931    Free PMC article.
Highly Cited.
Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo.
Andreas A Erdmann, Zhan-Guo Gao, +4 authors, Daniel H Fowler.
Blood, 2005 Mar 05; 105(12). PMID: 15746085    Free PMC article.
BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination.
Laurent Derré, Jean-Paul Rivals, +6 authors, Daniel E Speiser.
J Clin Invest, 2009 Dec 30; 120(1). PMID: 20038811    Free PMC article.
Highly Cited.
Galectin-9 in tumor biology: a jack of multiple trades.
Roy Heusschen, Arjan W Griffioen, Victor L Thijssen.
Biochim Biophys Acta, 2013 May 08; 1836(1). PMID: 23648450
A novel 80-kD cell surface structure identifies human circulating lymphocytes with natural killer activity.
H Maïza, G Leca, +3 authors, A Bensussan.
J Exp Med, 1993 Sep 01; 178(3). PMID: 7688788    Free PMC article.
CD200 as a prognostic factor in acute myeloid leukaemia.
A Tonks, R Hills, +4 authors, R L Darley.
Leukemia, 2007 Jan 26; 21(3). PMID: 17252007
CD155/PVR enhances glioma cell dispersal by regulating adhesion signaling and focal adhesion dynamics.
Kevin E Sloan, Jean K Stewart, +2 authors, Daniel G Jay.
Cancer Res, 2005 Dec 03; 65(23). PMID: 16322240
CD200: a putative therapeutic target in cancer.
Jérôme Moreaux, Jean Luc Veyrune, +2 authors, Bernard Klein.
Biochem Biophys Res Commun, 2007 Dec 07; 366(1). PMID: 18060862
Reciprocal expression of the TNF family receptor herpes virus entry mediator and its ligand LIGHT on activated T cells: LIGHT down-regulates its own receptor.
Y Morel, J M Schiano de Colella, +9 authors, R T Costello.
J Immunol, 2000 Oct 18; 165(8). PMID: 11035077
Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies.
Raanan Berger, Rinat Rotem-Yehudar, +6 authors, Arnon Nagler.
Clin Cancer Res, 2008 May 17; 14(10). PMID: 18483370
Highly Cited.
Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.
Haidong Dong, Scott E Strome, +10 authors, Lieping Chen.
Nat Med, 2002 Jul 02; 8(8). PMID: 12091876
Highly Cited.
Expression of the DNAM-1 ligands, Nectin-2 (CD112) and poliovirus receptor (CD155), on dendritic cells: relevance for natural killer-dendritic cell interaction.
Daniela Pende, Roberta Castriconi, +11 authors, Cristina Bottino.
Blood, 2005 Nov 24; 107(5). PMID: 16304049
Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis.
Yi Chen, Claire L Langrish, +10 authors, Daniel J Cua.
J Clin Invest, 2006 May 04; 116(5). PMID: 16670771    Free PMC article.
Highly Cited.
Systemic dysregulation of CEACAM1 in melanoma patients.
Gal Markel, Rona Ortenberg, +12 authors, Jacob Schachter.
Cancer Immunol Immunother, 2009 Jul 28; 59(2). PMID: 19633846
Study of the interaction of the medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28.
E R Follows, J C McPheat, +7 authors, W M Abbott.
Biochem J, 2001 Oct 05; 359(Pt 2). PMID: 11583591    Free PMC article.
Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease.
Silke Paust, Linrong Lu, Nami McCarty, Harvey Cantor.
Proc Natl Acad Sci U S A, 2004 Jul 06; 101(28). PMID: 15235129    Free PMC article.
The immune contexture in human tumours: impact on clinical outcome.
Wolf Herman Fridman, Franck Pagès, Catherine Sautès-Fridman, Jérôme Galon.
Nat Rev Cancer, 2012 Mar 16; 12(4). PMID: 22419253
Highly Cited. Review.
Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients.
Emanuela Romano, Monika Kusio-Kobialka, +7 authors, Daniel E Speiser.
Proc Natl Acad Sci U S A, 2015 Apr 29; 112(19). PMID: 25918390    Free PMC article.
Highly Cited.
Soluble human LAG-3 molecule amplifies the in vitro generation of type 1 tumor-specific immunity.
Chiara Casati, Chiara Camisaschi, +5 authors, Chiara Castelli.
Cancer Res, 2006 Apr 19; 66(8). PMID: 16618772
T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface.
Erhu Cao, Xingxing Zang, +12 authors, Steven C Almo.
Immunity, 2007 Mar 17; 26(3). PMID: 17363302
Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial.
Eugene D Kwon, Charles G Drake, +24 authors, CA184-043 Investigators.
Lancet Oncol, 2014 May 17; 15(7). PMID: 24831977    Free PMC article.
Highly Cited.
Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer.
Junzo Hamanishi, Masaki Mandai, +9 authors, Shingo Fujii.
Proc Natl Acad Sci U S A, 2007 Mar 16; 104(9). PMID: 17360651    Free PMC article.
Highly Cited.
B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma.
Scott E Strome, Haidong Dong, +10 authors, Lieping Chen.
Cancer Res, 2003 Oct 16; 63(19). PMID: 14559843
Highly Cited.
Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy.
Fumihiko Tsushima, Sheng Yao, +6 authors, Lieping Chen.
Blood, 2007 Feb 10; 110(1). PMID: 17289811    Free PMC article.
T cell intrinsic heterodimeric complexes between HVEM and BTLA determine receptivity to the surrounding microenvironment.
Timothy C Cheung, Lisa M Oborne, +10 authors, Carl F Ware.
J Immunol, 2009 Nov 17; 183(11). PMID: 19915044    Free PMC article.
CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells.
Sergio A Quezada, Karl S Peggs, Michael A Curran, James P Allison.
J Clin Invest, 2006 Jun 17; 116(7). PMID: 16778987    Free PMC article.
Highly Cited.
Expression and function of the B and T lymphocyte attenuator (BTLA/CD272) on human T cells.
Noriko Otsuki, Yousuke Kamimura, Masaaki Hashiguchi, Miyuki Azuma.
Biochem Biophys Res Commun, 2006 Apr 29; 344(4). PMID: 16643847
Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1.
Shigeki Chiba, Muhammad Baghdadi, +12 authors, Masahisa Jinushi.
Nat Immunol, 2012 Jul 31; 13(9). PMID: 22842346    Free PMC article.
Highly Cited.
Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer.
Yuichiro Ohigashi, Masayuki Sho, +12 authors, Yoshiyuki Nakajima.
Clin Cancer Res, 2005 Apr 20; 11(8). PMID: 15837746
Highly Cited.
Mice lacking CD200R1 show absence of suppression of lipopolysaccharide-induced tumor necrosis factor-alpha and mixed leukocyte culture responses by CD200.
Ivo Boudakov, Jian Liu, +3 authors, Reg M Gorczynski.
Transplantation, 2007 Aug 02; 84(2). PMID: 17667818
Biology and pathology of nectins and nectin-like molecules.
Toshiaki Sakisaka, Yoshimi Takai.
Curr Opin Cell Biol, 2004 Sep 15; 16(5). PMID: 15363801
Comprehensive molecular characterization of human colon and rectal cancer.
Cancer Genome Atlas Network.
Nature, 2012 Jul 20; 487(7407). PMID: 22810696    Free PMC article.
Highly Cited.
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
Caroline Robert, Luc Thomas, +21 authors, Jedd D Wolchok.
N Engl J Med, 2011 Jun 07; 364(26). PMID: 21639810
Highly Cited.
Convergent and divergent effects of costimulatory molecules in conventional and regulatory CD4+ T cells.
Ei Wakamatsu, Diane Mathis, Christophe Benoist.
Proc Natl Acad Sci U S A, 2013 Jan 02; 110(3). PMID: 23277554    Free PMC article.
Coinhibitory receptor PD-1H preferentially suppresses CD4⁺ T cell-mediated immunity.
Dallas B Flies, Xue Han, +4 authors, Lieping Chen.
J Clin Invest, 2014 Apr 20; 124(5). PMID: 24743150    Free PMC article.
Highly Cited.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits proximal TCR signaling by targeting ZAP-70.
Zhangguo Chen, Lanfen Chen, +2 authors, Richard S Blumberg.
J Immunol, 2008 Apr 22; 180(9). PMID: 18424730    Free PMC article.
PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1.
Marguerite Ghiotto, Laurent Gauthier, +4 authors, Daniel Olive.
Int Immunol, 2010 Jul 01; 22(8). PMID: 20587542    Free PMC article.
On being less tolerant: enhanced cancer immunosurveillance enabled by targeting checkpoints and agonists of T cell activation.
Alexander M Lesokhin, Margaret K Callahan, Michael A Postow, Jedd D Wolchok.
Sci Transl Med, 2015 Mar 27; 7(280). PMID: 25810313
Highly Cited. Review.
T cell/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells.
Rosemarie H DeKruyff, Xia Bu, +9 authors, José M Casasnovas.
J Immunol, 2010 Jan 20; 184(4). PMID: 20083673    Free PMC article.
Highly Cited.
Premature terminal exhaustion of Friend virus-specific effector CD8+ T cells by rapid induction of multiple inhibitory receptors.
Shiki Takamura, Sachiyo Tsuji-Kawahara, +5 authors, Masaaki Miyazawa.
J Immunol, 2010 Mar 31; 184(9). PMID: 20351188
B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion.
H Dong, G Zhu, K Tamada, L Chen.
Nat Med, 1999 Dec 02; 5(12). PMID: 10581077
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Analysis of the receptor-ligand interactions in the natural killer-mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the Poliovirus receptor (CD155) and Nectin-2 (CD112).
Daniela Pende, Grazia Maria Spaggiari, +11 authors, Lorenzo Moretta.
Blood, 2004 Nov 13; 105(5). PMID: 15536144
Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer.
Mario Sznol, Lieping Chen.
Clin Cancer Res, 2013 Mar 06; 19(5). PMID: 23460533    Free PMC article.
Highly Cited.
The blockade of immune checkpoints in cancer immunotherapy.
Drew M Pardoll.
Nat Rev Cancer, 2012 Mar 23; 12(4). PMID: 22437870    Free PMC article.
Highly Cited. Review.
Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma.
Andrew T Parsa, James S Waldron, +10 authors, Russell O Pieper.
Nat Med, 2006 Dec 13; 13(1). PMID: 17159987
Highly Cited.
Cutting edge: TIGIT has T cell-intrinsic inhibitory functions.
Nicole Joller, Jason P Hafler, +5 authors, Vijay K Kuchroo.
J Immunol, 2011 Jan 05; 186(3). PMID: 21199897    Free PMC article.
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Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways.
D Vercammen, G Brouckaert, +4 authors, P Vandenabeele.
J Exp Med, 1998 Sep 09; 188(5). PMID: 9730893    Free PMC article.
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VISTA Regulates the Development of Protective Antitumor Immunity.
Isabelle Le Mercier, Wenna Chen, +5 authors, Li Wang.
Cancer Res, 2014 Apr 03; 74(7). PMID: 24691994    Free PMC article.
Highly Cited.
Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity.
Philippe Le Bouteiller, Aliz Barakonyi, +9 authors, Armand Bensussan.
Proc Natl Acad Sci U S A, 2002 Dec 18; 99(26). PMID: 12486241    Free PMC article.
CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1.
Julien Fourcade, Zhaojun Sun, +7 authors, Hassane M Zarour.
Cancer Res, 2011 Dec 30; 72(4). PMID: 22205715    Free PMC article.
Highly Cited.
TIM-3 does not act as a receptor for galectin-9.
Judith Leitner, Armin Rieger, +3 authors, Peter Steinberger.
PLoS Pathog, 2013 Apr 05; 9(3). PMID: 23555261    Free PMC article.
LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes.
L Meyaard, G J Adema, +4 authors, J H Phillips.
Immunity, 1997 Aug 01; 7(2). PMID: 9285412
Suppression of antigen-specific T cell responses by the Kaposi's sarcoma-associated herpesvirus viral OX2 protein and its cellular orthologue, CD200.
Karen Misstear, Simon A Chanas, +7 authors, David J Blackbourn.
J Virol, 2012 Apr 12; 86(11). PMID: 22491458    Free PMC article.
Management of immune-related adverse events and kinetics of response with ipilimumab.
Jeffrey S Weber, Katharina C Kähler, Axel Hauschild.
J Clin Oncol, 2012 May 23; 30(21). PMID: 22614989
Highly Cited. Review.
Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies.
Karl S Peggs, Sergio A Quezada, +2 authors, James P Allison.
J Exp Med, 2009 Jul 08; 206(8). PMID: 19581407    Free PMC article.
Highly Cited.
Immunofluorescence analysis of poliovirus receptor expression in Peyer's patches of humans, primates, and CD155 transgenic mice: implications for poliovirus infection.
Akiko Iwasaki, Reinhold Welker, +3 authors, Eckard Wimmer.
J Infect Dis, 2002 Aug 27; 186(5). PMID: 12195344
Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1.
Hideki Iijima, Markus F Neurath, +11 authors, Richard S Blumberg.
J Exp Med, 2004 Feb 19; 199(4). PMID: 14970176    Free PMC article.
Regulatory T cell expression of herpesvirus entry mediator suppresses the function of B and T lymphocyte attenuator-positive effector T cells.
Ran Tao, Liqing Wang, +2 authors, Wayne W Hancock.
J Immunol, 2008 May 06; 180(10). PMID: 18453584
Leukocyte-associated Ig-like receptor-1 has SH2 domain-containing phosphatase-independent function and recruits C-terminal Src kinase.
Annelies Verbrugge, Eva S K Rijkers, Talitha de Ruiter, Linde Meyaard.
Eur J Immunol, 2005 Dec 29; 36(1). PMID: 16380958
Comprehensive genomic characterization of squamous cell lung cancers.
Cancer Genome Atlas Research Network.
Nature, 2012 Sep 11; 489(7417). PMID: 22960745    Free PMC article.
Highly Cited.
CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity.
Gal Markel, Niva Lieberman, +8 authors, Ofer Mandelboim.
J Immunol, 2002 Mar 09; 168(6). PMID: 11884449
T-cell immunoglobulin and ITIM domain (TIGIT) receptor/poliovirus receptor (PVR) ligand engagement suppresses interferon-γ production of natural killer cells via β-arrestin 2-mediated negative signaling.
Man Li, Pengyan Xia, +10 authors, Zusen Fan.
J Biol Chem, 2014 May 13; 289(25). PMID: 24817116    Free PMC article.
A new role of CTLA-4 on B cells in thymus-dependent immune responses in vivo.
Dagmar Quandt, Holger Hoff, +2 authors, Monika C Brunner-Weinzierl.
J Immunol, 2007 Nov 21; 179(11). PMID: 18025174
TIM-3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines.
William D Hastings, David E Anderson, +7 authors, Vijay K Kuchroo.
Eur J Immunol, 2009 Aug 14; 39(9). PMID: 19676072    Free PMC article.
Highly Cited.
Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway.
Yumiko Kashio, Kazuhiro Nakamura, +5 authors, Mitsuomi Hirashima.
J Immunol, 2003 Mar 21; 170(7). PMID: 12646627
Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity.
Fumiya Hirano, Katsumi Kaneko, +9 authors, Lieping Chen.
Cancer Res, 2005 Feb 12; 65(3). PMID: 15705911
Highly Cited.
A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells.
Paul E Zarek, Ching-Tai Huang, +5 authors, Jonathan D Powell.
Blood, 2007 Oct 03; 111(1). PMID: 17909080    Free PMC article.
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PD-L2 is expressed on activated human T cells and regulates their function.
Nassima Messal, Nacer-Eddine Serriari, +2 authors, Daniel Olive.
Mol Immunol, 2011 Jul 15; 48(15-16). PMID: 21752471
The inhibitory leukocyte-associated Ig-like receptor-1 (LAIR-1) is expressed at high levels by human naive T cells and inhibits TCR mediated activation.
Kerima Maasho, Madhan Masilamani, +3 authors, Francisco Borrego.
Mol Immunol, 2005 Jun 14; 42(12). PMID: 15950745
Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease.
Laurent Monney, Catherine A Sabatos, +9 authors, Vijay K Kuchroo.
Nature, 2002 Feb 02; 415(6871). PMID: 11823861
Highly Cited.
Activation of the adenosine A2A receptor attenuates experimental autoimmune myasthenia gravis severity.
Na Li, Lili Mu, +12 authors, Hulun Li.
Eur J Immunol, 2012 Apr 28; 42(5). PMID: 22539289
Optimal ratios of biliary glycoprotein isoforms required for inhibition of colonic tumor cell growth.
C Turbide, T Kunath, E Daniels, N Beauchemin.
Cancer Res, 1997 Jul 01; 57(13). PMID: 9205090
An immunoadhesin incorporating the molecule OX-2 is a potent immunosuppressant that prolongs allo- and xenograft survival.
R M Gorczynski, M S Cattral, +5 authors, J Ni.
J Immunol, 1999 Jul 22; 163(3). PMID: 10415071
Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes.
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Nat Immunol, 2002 Feb 19; 3(3). PMID: 11850628
Highly Cited.
Receptors that interact with nectin and nectin-like proteins in the immunosurveillance and immunotherapy of cancer.
Christopher J Chan, Daniel M Andrews, Mark J Smyth.
Curr Opin Immunol, 2012 Jan 31; 24(2). PMID: 22285893
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Leukemia, 2003 Oct 17; 17(12). PMID: 14562115
B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator.
John R Sedy, Maya Gavrieli, +8 authors, Kenneth M Murphy.
Nat Immunol, 2004 Nov 30; 6(1). PMID: 15568026
Highly Cited.
The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function.
Robert J Johnston, Laetitia Comps-Agrar, +9 authors, Jane L Grogan.
Cancer Cell, 2014 Dec 04; 26(6). PMID: 25465800
Highly Cited.
Cutting edge: molecular analysis of the negative regulatory function of lymphocyte activation gene-3.
Creg J Workman, Kari J Dugger, Dario A A Vignali.
J Immunol, 2002 Nov 08; 169(10). PMID: 12421911
PD-L2 is a second ligand for PD-1 and inhibits T cell activation.
Y Latchman, C R Wood, +18 authors, G J Freeman.
Nat Immunol, 2001 Feb 27; 2(3). PMID: 11224527
Highly Cited.
Collagens are functional, high affinity ligands for the inhibitory immune receptor LAIR-1.
Robert Jan Lebbink, Talitha de Ruiter, +8 authors, Linde Meyaard.
J Exp Med, 2006 Jun 07; 203(6). PMID: 16754721    Free PMC article.
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity.
Kaori Sakuishi, Lionel Apetoh, +3 authors, Ana C Anderson.
J Exp Med, 2010 Sep 08; 207(10). PMID: 20819927    Free PMC article.
Highly Cited.
CD200 is a ligand for all members of the CD200R family of immunoregulatory molecules.
Reginald Gorczynski, Zhiqi Chen, +3 authors, Philip A Marsden.
J Immunol, 2004 Jun 10; 172(12). PMID: 15187158
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells.
Loise M Francisco, Victor H Salinas, +4 authors, Arlene H Sharpe.
J Exp Med, 2009 Dec 17; 206(13). PMID: 20008522    Free PMC article.
Highly Cited.
Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization.
Lukas Baitsch, Amandine Legat, +11 authors, Daniel E Speiser.
PLoS One, 2012 Feb 22; 7(2). PMID: 22347406    Free PMC article.
Highly Cited.
A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells.
Courtney M Lappas, Jayson M Rieger, Joel Linden.
J Immunol, 2005 Jan 07; 174(2). PMID: 15634932
Highly Cited.
Murine CD160, Ig-like receptor on NK cells and NKT cells, recognizes classical and nonclassical MHC class I and regulates NK cell activation.
Motoi Maeda, Carmine Carpenito, +6 authors, Fumio Takei.
J Immunol, 2005 Sep 24; 175(7). PMID: 16177084
The unusual distribution of the neuronal/lymphoid cell surface CD200 (OX2) glycoprotein is conserved in humans.
G J Wright, M Jones, +2 authors, A N Barclay.
Immunology, 2001 Mar 22; 102(2). PMID: 11260322    Free PMC article.
Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors.
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Annu Rev Immunol, 2004 Mar 23; 22. PMID: 15032592
Highly Cited. Review.
Regulation of T cell responses by the receptor molecule Tim-3.
Jacob V Gorman, John D Colgan.
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J Immunol, 2002 Jan 22; 168(3). PMID: 11801635
Differential and tumor-specific expression of CD160 in B-cell malignancies.
Timothy W Farren, Jerome Giustiniani, +11 authors, Samir G Agrawal.
Blood, 2011 Jul 01; 118(8). PMID: 21715317    Free PMC article.
Confusing signals: recent progress in CTLA-4 biology.
Lucy S K Walker, David M Sansom.
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Highly Cited. Review.
Molecular pathways: next-generation immunotherapy--inhibiting programmed death-ligand 1 and programmed death-1.
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Clin Cancer Res, 2012 Oct 23; 18(24). PMID: 23087408
Highly Cited.
PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells.
Kim L Good-Jacobson, Courtney G Szumilas, +3 authors, Mark J Shlomchik.
Nat Immunol, 2010 May 11; 11(6). PMID: 20453843    Free PMC article.
Highly Cited.
Pivotal role of CEACAM1 protein in the inhibition of activated decidual lymphocyte functions.
Gal Markel, Dana Wolf, +5 authors, Ofer Mandelboim.
J Clin Invest, 2002 Oct 09; 110(7). PMID: 12370272    Free PMC article.
A disintegrin and metalloprotease (ADAM) 10 and ADAM17 are major sheddases of T cell immunoglobulin and mucin domain 3 (Tim-3).
Katja Möller-Hackbarth, Christin Dewitz, +4 authors, Jürgen Scheller.
J Biol Chem, 2013 Oct 15; 288(48). PMID: 24121505    Free PMC article.
Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3+CD4+ regulatory T cells.
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Highly Cited.
Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy.
Bronwen R Burton, Graham J Britton, +7 authors, David C Wraith.
Nat Commun, 2014 Sep 04; 5. PMID: 25182274    Free PMC article.
CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism.
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Attenuating lymphocyte activity: the crystal structure of the BTLA-HVEM complex.
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B and T lymphocyte attenuator-mediated signal transduction provides a potent inhibitory signal to primary human CD4 T cells that can be initiated by multiple phosphotyrosine motifs.
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J Immunol, 2006 May 20; 176(11). PMID: 16709818
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
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HVEM expression contributes to tumor progression and prognosis in human colorectal cancer.
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J Immunol, 2005 Apr 09; 174(8). PMID: 15814706
Carcinoembryonic antigen-related cell adhesion molecule 1 expression and signaling in human, mouse, and rat leukocytes: evidence for replacement of the short cytoplasmic domain isoform by glycosylphosphatidylinositol-linked proteins in human leukocytes.
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J Immunol, 2002 May 08; 168(10). PMID: 11994468
Negative regulation of T cell homeostasis by lymphocyte activation gene-3 (CD223).
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J Immunol, 2005 Jan 07; 174(2). PMID: 15634887
CD200 expression on tumor cells suppresses antitumor immunity: new approaches to cancer immunotherapy.
Anke Kretz-Rommel, Fenghua Qin, +10 authors, Katherine S Bowdish.
J Immunol, 2007 Apr 20; 178(9). PMID: 17442942
Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion.
Manu Rangachari, Chen Zhu, +13 authors, Vijay K Kuchroo.
Nat Med, 2012 Aug 07; 18(9). PMID: 22863785    Free PMC article.
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Down-regulation of CEACAM1 in human prostate cancer: correlation with loss of cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition.
Christer Busch, Tor Arne Hanssen, Christoph Wagener, Björn OBrink.
Hum Pathol, 2002 Apr 30; 33(3). PMID: 11979369
The human poliovirus receptor related 2 protein is a new hematopoietic/endothelial homophilic adhesion molecule.
M Lopez, M Aoubala, +3 authors, P Dubreuil.
Blood, 1998 Dec 09; 92(12). PMID: 9845526
The short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal immunity and homeostasis via Tfh cell induction.
Lanfen Chen, Zhangguo Chen, +19 authors, Richard S Blumberg.
Immunity, 2012 Nov 06; 37(5). PMID: 23123061    Free PMC article.
T cell Ig and mucin domain-containing protein 3 is recruited to the immune synapse, disrupts stable synapse formation, and associates with receptor phosphatases.
Kiera L Clayton, Matthew S Haaland, +4 authors, Mario A Ostrowski.
J Immunol, 2013 Dec 18; 192(2). PMID: 24337741    Free PMC article.
Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance.
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Nat Immunol, 2003 Oct 14; 4(11). PMID: 14556005
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High expression of the inhibitory receptor BTLA in T-follicular helper cells and in B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia.
Hasni M'Hidi, Marie-Laure Thibult, +5 authors, Luc Xerri.
Am J Clin Pathol, 2009 Sep 19; 132(4). PMID: 19762537
Soluble form of T cell Ig mucin 3 is an inhibitory molecule in T cell-mediated immune response.
Hui Geng, Gui-Mei Zhang, +6 authors, Zuo-Hua Feng.
J Immunol, 2006 Jan 21; 176(3). PMID: 16424168
Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.
Omid Hamid, Caroline Robert, +23 authors, Antoni Ribas.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724846    Free PMC article.
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CD200 and membrane protein interactions in the control of myeloid cells.
A Neil Barclay, Gavin J Wright, Gary Brooke, Marion H Brown.
Trends Immunol, 2002 Jun 20; 23(6). PMID: 12072366
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PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
Stephen M Ansell, Alexander M Lesokhin, +16 authors, Philippe Armand.
N Engl J Med, 2014 Dec 09; 372(4). PMID: 25482239    Free PMC article.
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Comprehensive galectin fingerprinting in a panel of 61 human tumor cell lines by RT-PCR and its implications for diagnostic and therapeutic procedures.
H Lahm, S André, +5 authors, H J Gabius.
J Cancer Res Clin Oncol, 2001 Jun 21; 127(6). PMID: 11414198
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J Leukoc Biol, 2009 Dec 17; 87(2). PMID: 20007250
Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells.
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J Immunol, 2009 Oct 06; 183(8). PMID: 19801517
Enhancement of antitumor immunity by CTLA-4 blockade.
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Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection.
R Brad Jones, Lishomwa C Ndhlovu, +24 authors, Mario A Ostrowski.
J Exp Med, 2008 Nov 13; 205(12). PMID: 19001139    Free PMC article.
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Adenosine receptors: therapeutic aspects for inflammatory and immune diseases.
György Haskó, Joel Linden, Bruce Cronstein, Pál Pacher.
Nat Rev Drug Discov, 2008 Sep 02; 7(9). PMID: 18758473    Free PMC article.
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Restoring immune function of tumor-specific CD4+ T cells during recurrence of melanoma.
Stephen R Goding, Kyle A Wilson, +7 authors, Paul Andrew Antony.
J Immunol, 2013 Mar 29; 190(9). PMID: 23536636    Free PMC article.
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Galectin-9/TIM-3 interaction regulates virus-specific primary and memory CD8 T cell response.
Sharvan Sehrawat, Pradeep B J Reddy, +3 authors, Barry T Rouse.
PLoS Pathog, 2010 May 14; 6(5). PMID: 20463811    Free PMC article.
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B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma.
Ilona Kryczek, Linhua Zou, +12 authors, Weiping Zou.
J Exp Med, 2006 Apr 12; 203(4). PMID: 16606666    Free PMC article.
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Cancer immunotherapy: Strategies for personalization and combinatorial approaches.
Vishwanath Sathyanarayanan, Sattva S Neelapu.
Mol Oncol, 2015 Nov 10; 9(10). PMID: 26548534    Free PMC article.
T-cell receptor gene therapy--ready to go viral?
Terhi Karpanen, Johanna Olweus.
Mol Oncol, 2015 Nov 10; 9(10). PMID: 26548533    Free PMC article.
Impaired Subset Progression and Polyfunctionality of T Cells in Mice Exposed to Methamphetamine during Chronic LCMV Infection.
Uma Sriram, Beth L Hill, +4 authors, Raghava Potula.
PLoS One, 2016 Oct 21; 11(10). PMID: 27760221    Free PMC article.
Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells.
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Immunity, 2016 Nov 17; 45(5). PMID: 27851914    Free PMC article.
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Human Papillomavirus Drives Tumor Development Throughout the Head and Neck: Improved Prognosis Is Associated With an Immune Response Largely Restricted to the Oropharynx.
Ankur Chakravarthy, Stephen Henderson, +6 authors, Tim R Fenton.
J Clin Oncol, 2016 Nov 20; 34(34). PMID: 27863190    Free PMC article.
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Exceptional Response to Nivolumab and Stereotactic Body Radiation Therapy (SBRT) in Neuroendocrine Cervical Carcinoma with High Tumor Mutational Burden: Management Considerations from the Center For Personalized Cancer Therapy at UC San Diego Moores Cancer Center.
Andrew Sharabi, Sangwoo Shawn Kim, +5 authors, Razelle Kurzrock.
Oncologist, 2017 May 28; 22(6). PMID: 28550027    Free PMC article.
Potency-matched Dual Cytokine-Antibody Fusion Proteins for Cancer Therapy.
Roberto De Luca, Alex Soltermann, +4 authors, Dario Neri.
Mol Cancer Ther, 2017 Jul 19; 16(11). PMID: 28716814    Free PMC article.
Coinhibitory Receptor Expression and Immune Checkpoint Blockade: Maintaining a Balance in CD8+ T Cell Responses to Chronic Viral Infections and Cancer.
Isobel S Okoye, Michael Houghton, +2 authors, Shokrollah Elahi.
Front Immunol, 2017 Oct 17; 8. PMID: 29033936    Free PMC article.
CTLA-4+PD-1- Memory CD4+ T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques.
Colleen S McGary, Claire Deleage, +14 authors, Mirko Paiardini.
Immunity, 2017 Oct 19; 47(4). PMID: 29045906    Free PMC article.
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Immune checkpoint inhibitors: new strategies to checkmate cancer.
R A M Wilson, T R J Evans, A R Fraser, R J B Nibbs.
Clin Exp Immunol, 2017 Nov 16; 191(2). PMID: 29139554    Free PMC article.
Importance of immune monitoring approaches and the use of immune checkpoints for the treatment of diffuse intrinsic pontine glioma: From bench to clinic and vice versa (Review).
Jorge Augusto Borin Scutti.
Int J Oncol, 2018 Feb 28; 52(4). PMID: 29484440    Free PMC article.
Cancer epigenetics: Moving forward.
Angela Nebbioso, Francesco Paolo Tambaro, Carmela Dell'Aversana, Lucia Altucci.
PLoS Genet, 2018 Jun 08; 14(6). PMID: 29879107    Free PMC article.
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High-affinity PD-1 molecules deliver improved interaction with PD-L1 and PD-L2.
Yanyan Li, Zhaoduan Liang, +9 authors, Yi Li.
Cancer Sci, 2018 Jun 12; 109(8). PMID: 29890018    Free PMC article.
The role of automated cytometry in the new era of cancer immunotherapy.
Marco Danova, Martina Torchio, +3 authors, Giuliano Mazzini.
Mol Clin Oncol, 2018 Sep 21; 9(4). PMID: 30233791    Free PMC article.
Clinicopathologic and microenvironmental analysis of primary cutaneous CD30-positive lymphoproliferative disorders: a 26 year experience from an academic medical center in Brazil.
Cristiane Rúbia Ferreira, Shuchun Zhao, +6 authors, Dita Gratzinger.
Diagn Pathol, 2019 Oct 24; 14(1). PMID: 31640798    Free PMC article.
The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation.
Anne Månsson Kvarnhammar, Niina Veitonmäki, +16 authors, Peter Ellmark.
J Immunother Cancer, 2019 Apr 13; 7(1). PMID: 30975201    Free PMC article.
Loss of BAP1 expression is associated with an immunosuppressive microenvironment in uveal melanoma, with implications for immunotherapy development.
Carlos R Figueiredo, Helen Kalirai, +5 authors, Sarah E Coupland.
J Pathol, 2020 Jan 22; 250(4). PMID: 31960425    Free PMC article.
Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma.
Hanjie Li, Anne M van der Leun, +15 authors, Ido Amit.
Cell, 2019 Jan 01; 176(4). PMID: 30595452    Free PMC article.
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Optimizing Oncolytic Viral Design to Enhance Antitumor Efficacy: Progress and Challenges.
Shyambabu Chaurasiya, Yuman Fong, Susanne G Warner.
Cancers (Basel), 2020 Jul 02; 12(6). PMID: 32604787    Free PMC article.
Impact of Diet and Nutrition on Cancer Hallmarks.
Karen L Chen, Paul Jung, +8 authors, Zeynep Madak-Erdogan.
J Cancer Prev Curr Res, 2017 Jan 01; 7(4). PMID: 30581989    Free PMC article.
The Therapeutic Strategies of Regulatory T Cells in Malignancies and Stem Cell Transplantations.
Rana G Zaini, Amani A Al-Rehaili.
J Oncol, 2019 Jan 30; 2019. PMID: 30693029    Free PMC article.
Editorial: Management of Immune-Related Adverse Events for Patients Undergoing Treatment With Checkpoint Inhibitors.
Bernardo Leon Rapoport.
Front Oncol, 2019 Jun 04; 9. PMID: 31157163    Free PMC article.
Rational Combination of Parvovirus H1 With CTLA-4 and PD-1 Checkpoint Inhibitors Dampens the Tumor Induced Immune Silencing.
Katrin Goepfert, Christiane Dinsart, +2 authors, Markus Moehler.
Front Oncol, 2019 Jun 14; 9. PMID: 31192129    Free PMC article.
Contributions of T cell dysfunction to the resistance against anti-PD-1 therapy in oral carcinogenesis.
Liling Wen, Huanzi Lu, +8 authors, Zhi Wang.
J Exp Clin Cancer Res, 2019 Jul 12; 38(1). PMID: 31291983    Free PMC article.
Negative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy.
Anna Śledzińska, Laurie Menger, +2 authors, Sergio A Quezada.
Mol Oncol, 2015 Nov 19; 9(10). PMID: 26578451    Free PMC article.
Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.
Andrea Ponzetta, Roberta Carriero, +20 authors, Sebastien Jaillon.
Cell, 2019 Jul 02; 178(2). PMID: 31257026    Free PMC article.
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PD-1 Immune Checkpoint Inhibitor Therapy Malignant Tumor Based on Monotherapy and Combined Treatment Research.
Yu Zhang, Guang-Ze Mou, +7 authors, Cheng-Hao Jin.
Technol Cancer Res Treat, 2021 Mar 25; 20. PMID: 33759637    Free PMC article.
DGKζ exerts greater control than DGKα over CD8+ T cell activity and tumor inhibition.
Junchen Gu, Cindy Wang, +9 authors, Matthew J Riese.
Oncoimmunology, 2021 Aug 06; 10(1). PMID: 34350062    Free PMC article.
Differences in Immune Checkpoints Expression (TIM-3 and PD-1) on T Cells in Women with Recurrent Miscarriages-Preliminary Studies.
Michał Zych, Aleksander Roszczyk, +2 authors, Radosław Zagożdżon.
J Clin Med, 2021 Sep 29; 10(18). PMID: 34575293    Free PMC article.
Hodgkin Lymphoma: A Special Microenvironment.
Giuseppina Opinto, Claudio Agostinelli, +3 authors, Giuseppe Ingravallo.
J Clin Med, 2021 Oct 24; 10(20). PMID: 34682791    Free PMC article.
Expression Profiles and Prognostic Value of Multiple Inhibitory Checkpoints in Head and Neck Lymphoepithelioma-Like Carcinoma.
Wen-Qing Zou, Wei-Jie Luo, +7 authors, Yan-Ping Mao.
Front Immunol, 2022 Feb 11; 13. PMID: 35140722    Free PMC article.
Insights Into Persistent HIV-1 Infection and Functional Cure: Novel Capabilities and Strategies.
Tram M Ta, Sajjaf Malik, +6 authors, Taisuke Izumi.
Front Microbiol, 2022 May 17; 13. PMID: 35572626    Free PMC article.