. 2019 Sep; 2055:23-60.
doi: 10.1007/978-1-4939-9773-2_2.

Immunological Targets for Immunotherapy: Inhibitory T Cell Receptors

Diwakar Davar 1 Hassane M Zarour 2 
  • PMID: 31502146
  •     172 References
  •     2 citations


Tumor development is characterized by the accumulation of mutational and epigenetic changes that transform normal cells and survival pathways into self-sustaining cells capable of untrammeled growth. Although multiple modalities including surgery, radiation, and chemotherapy are available for the treatment of cancer, the benefits conferred are often limited. The immune system is capable of specific, durable, and adaptable responses. However, cancers hijack immune mechanisms such as negative regulatory checkpoints that have evolved to limit inflammatory and immune responses to thwart effective antitumor immunity. The development of monoclonal antibodies against inhibitory receptors expressed by immune cells has produced durable responses in a broad array of advanced malignancies and heralded a new dawn in the cancer armamentarium. However, these remarkable responses are limited to a minority of patients and indications, highlighting the need for more effective and novel approaches. Preclinical and clinical studies with immune checkpoint blockade are exploring the therapeutic potential antibody-based therapy targeting multiple inhibitory receptors. In this chapter, we discuss the current understanding of the structure, ligand specificities, function, and signaling activities of various inhibitory receptors. Additionally, we discuss the current development status of various immune checkpoint inhibitors targeting these negative immune receptors and highlight conceptual gaps in knowledge.

Keywords: BTLA; CTLA-4; Immunotherapy; Inhibitory receptors; LAG-3; PD-1; TIGIT; TIM-3; VISTA.

Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma.
Dirk Schadendorf, F Stephen Hodi, +7 authors, Jedd D Wolchok.
J Clin Oncol, 2015 Feb 11; 33(17). PMID: 25667295    Free PMC article.
Highly Cited.
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.
Padmanee Sharma, Siwen Hu-Lieskovan, Jennifer A Wargo, Antoni Ribas.
Cell, 2017 Feb 12; 168(4). PMID: 28187290    Free PMC article.
Highly Cited. Review.
Delineation of an extended surface contact area on human CD4 involved in class II major histocompatibility complex binding.
U Moebius, P Pallai, S C Harrison, E L Reinherz.
Proc Natl Acad Sci U S A, 1993 Sep 01; 90(17). PMID: 8367491    Free PMC article.
Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens.
Matthew M Gubin, Xiuli Zhang, +24 authors, Robert D Schreiber.
Nature, 2014 Nov 28; 515(7528). PMID: 25428507    Free PMC article.
Highly Cited.
LAG-3, a novel lymphocyte activation gene closely related to CD4.
F Triebel, S Jitsukawa, +4 authors, T Hercend.
J Exp Med, 1990 May 01; 171(5). PMID: 1692078    Free PMC article.
Highly Cited.
CEACAM1 regulates TIM-3-mediated tolerance and exhaustion.
Yu-Hwa Huang, Chen Zhu, +21 authors, Richard S Blumberg.
Nature, 2014 Nov 05; 517(7534). PMID: 25363763    Free PMC article.
Highly Cited.
A regulatory role for cytoplasmic YVKM motif in CTLA-4 inhibition of TCR signaling.
H Schneider, S da Rocha Dias, H Hu, C E Rudd.
Eur J Immunol, 2001 Jul 13; 31(7). PMID: 11449357
Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo.
Giorgia Rota, Charlène Niogret, +8 authors, Greta Guarda.
Cell Rep, 2018 Apr 05; 23(1). PMID: 29617671
Highly Cited.
T cell exhaustion.
E John Wherry.
Nat Immunol, 2011 Jul 09; 12(6). PMID: 21739672
Highly Cited. Review.
Myeloid derived suppressor cells - a new therapeutic target in the treatment of cancer.
Robert Wesolowski, Joseph Markowitz, William E Carson.
J Immunother Cancer, 2013 Jan 01; 1. PMID: 24829747    Free PMC article.
Highly Cited. Review.
The cytoplasmic domain of CD28 is both necessary and sufficient for costimulation of interleukin-2 secretion and association with phosphatidylinositol 3'-kinase.
P H Stein, J D Fraser, A Weiss.
Mol Cell Biol, 1994 May 01; 14(5). PMID: 8164687    Free PMC article.
CD96 targeted antibodies need not block CD96-CD155 interactions to promote NK cell anti-metastatic activity.
Amelia Roman Aguilera, Viviana P Lutzky, +7 authors, Mark J Smyth.
Oncoimmunology, 2018 May 04; 7(5). PMID: 29721390    Free PMC article.
The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation.
Wenwen Xu, TạMinh Hiếu, Subramaniam Malarkannan, Li Wang.
Cell Mol Immunol, 2018 Jan 30; 15(5). PMID: 29375120    Free PMC article.
Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family.
J J McIntire, S E Umetsu, +6 authors, R H DeKruyff.
Nat Immunol, 2001 Nov 29; 2(12). PMID: 11725301
Highly Cited.
IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade.
Mark Ayers, Jared Lunceford, +12 authors, Terrill K McClanahan.
J Clin Invest, 2017 Jun 27; 127(8). PMID: 28650338    Free PMC article.
Highly Cited.
PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients.
Julien Fourcade, Pavol Kudela, +9 authors, Hassane M Zarour.
J Immunol, 2009 Apr 22; 182(9). PMID: 19380770    Free PMC article.
Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4.
E A Tivol, F Borriello, +3 authors, A H Sharpe.
Immunity, 1995 Nov 01; 3(5). PMID: 7584144
Highly Cited.
Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.
Antoni Ribas, Richard Kefford, +21 authors, Axel Hauschild.
J Clin Oncol, 2013 Jan 09; 31(5). PMID: 23295794    Free PMC article.
Highly Cited.
Lack of TIM-3 immunoregulation in multiple sclerosis.
Li Yang, David E Anderson, Juhi Kuchroo, David A Hafler.
J Immunol, 2008 Mar 21; 180(7). PMID: 18354161
Lymphocyte-activation gene 3/major histocompatibility complex class II interaction modulates the antigenic response of CD4+ T lymphocytes.
B Huard, M Tournier, +2 authors, F Faure.
Eur J Immunol, 1994 Dec 01; 24(12). PMID: 7805750
Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens.
E Baixeras, B Huard, +6 authors, D Piatier-Tonneau.
J Exp Med, 1992 Aug 01; 176(2). PMID: 1380059    Free PMC article.
Highly Cited.
PD-1 promotes immune exhaustion by inducing antiviral T cell motility paralysis.
Bernd H Zinselmeyer, Sara Heydari, +7 authors, Dorian B McGavern.
J Exp Med, 2013 Mar 27; 210(4). PMID: 23530125    Free PMC article.
Highly Cited.
Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer.
Lin Zhang, Jose R Conejo-Garcia, +9 authors, George Coukos.
N Engl J Med, 2003 Jan 17; 348(3). PMID: 12529460
Highly Cited.
PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation.
Nikolaos Patsoukis, Kankana Bardhan, +9 authors, Vassiliki A Boussiotis.
Nat Commun, 2015 Mar 27; 6. PMID: 25809635    Free PMC article.
Highly Cited.
Type, density, and location of immune cells within human colorectal tumors predict clinical outcome.
Jérôme Galon, Anne Costes, +13 authors, Franck Pagès.
Science, 2006 Sep 30; 313(5795). PMID: 17008531
Highly Cited.
Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses.
Spencer C Liang, Yvette E Latchman, +4 authors, Arlene H Sharpe.
Eur J Immunol, 2003 Sep 30; 33(10). PMID: 14515254
Highly Cited.
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells.
Mark J Selby, John J Engelhardt, +4 authors, Alan J Korman.
Cancer Immunol Res, 2014 Apr 30; 1(1). PMID: 24777248
Highly Cited.
Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation.
A van Elsas, A A Hurwitz, J P Allison.
J Exp Med, 1999 Aug 03; 190(3). PMID: 10430624    Free PMC article.
Highly Cited.
B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells.
S Y Tseng, M Otsuji, +7 authors, H Tsuchiya.
J Exp Med, 2001 Apr 03; 193(7). PMID: 11283156    Free PMC article.
Highly Cited.
Cytotoxic T lymphocyte antigen 4 (CTLA-4) interferes with extracellular signal-regulated kinase (ERK) and Jun NH2-terminal kinase (JNK) activation, but does not affect phosphorylation of T cell receptor zeta and ZAP70.
C R Calvo, D Amsen, A M Kruisbeek.
J Exp Med, 1997 Dec 31; 186(10). PMID: 9362525    Free PMC article.
CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling.
S Hannier, M Tournier, G Bismuth, F Triebel.
J Immunol, 1998 Oct 21; 161(8). PMID: 9780176
Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade.
Spencer C Wei, Jacob H Levine, +8 authors, James P Allison.
Cell, 2017 Aug 15; 170(6). PMID: 28803728    Free PMC article.
Highly Cited.
LAG-3 regulates plasmacytoid dendritic cell homeostasis.
Creg J Workman, Yao Wang, +4 authors, Dario A A Vignali.
J Immunol, 2009 Feb 10; 182(4). PMID: 19201841    Free PMC article.
Uncovering of functional alternative CTLA-4 counter-receptor in B7-deficient mice.
G J Freeman, F Borriello, +7 authors, D B Lombard.
Science, 1993 Nov 05; 262(5135). PMID: 7694362
Highly Cited.
BTLA identifies dysfunctional PD-1-expressing CD4+ T cells in human hepatocellular carcinoma.
Qiyi Zhao, Zhan-Lian Huang, +2 authors, Dong-Ming Kuang.
Oncoimmunology, 2017 Jan 27; 5(12). PMID: 28123898    Free PMC article.
Cancer Cell-Intrinsic PD-1 and Implications in Combinatorial Immunotherapy.
Han Yao, Huanbin Wang, +2 authors, Jie Xu.
Front Immunol, 2018 Aug 15; 9. PMID: 30105035    Free PMC article.
Progression of Lung Cancer Is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors.
Daniela S Thommen, Jens Schreiner, +14 authors, Alfred Zippelius.
Cancer Immunol Res, 2015 Aug 09; 3(12). PMID: 26253731
Highly Cited.
Vstm3 is a member of the CD28 family and an important modulator of T-cell function.
Steven D Levin, David W Taft, +21 authors, Katherine E Lewis.
Eur J Immunol, 2011 Mar 19; 41(4). PMID: 21416464    Free PMC article.
Cancer Tumor antigens.
Boon, Old.
Curr Opin Immunol, 1998 Jan 24; 9(5). PMID: 9438857
CTLA-4 disrupts ZAP70 microcluster formation with reduced T cell/APC dwell times and calcium mobilization.
Helga Schneider, Xin Smith, +2 authors, Christopher E Rudd.
Eur J Immunol, 2007 Dec 21; 38(1). PMID: 18095376    Free PMC article.
Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.
Frederick Arce Vargas, Andrew J S Furness, +32 authors, Sergio A Quezada.
Cancer Cell, 2018 Mar 27; 33(4). PMID: 29576375    Free PMC article.
Highly Cited.
T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1.
P S Linsley, E A Clark, J A Ledbetter.
Proc Natl Acad Sci U S A, 1990 Jul 01; 87(13). PMID: 2164219    Free PMC article.
Highly Cited.
Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation.
Nikolaos Patsoukis, Julia Brown, +3 authors, Vassiliki A Boussiotis.
Sci Signal, 2012 Jun 29; 5(230). PMID: 22740686    Free PMC article.
Highly Cited.
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
Highly Cited.
Mutational analysis of the interaction between CD4 and class II MHC: class II antigens contact CD4 on a surface opposite the gp120-binding site.
S Fleury, D Lamarre, +4 authors, R P Sekaly.
Cell, 1991 Sep 06; 66(5). PMID: 1889086
Unexpected role of B and T lymphocyte attenuator in sustaining cell survival during chronic allostimulation.
Michelle A Hurchla, John R Sedy, Kenneth M Murphy.
J Immunol, 2007 May 04; 178(10). PMID: 17475832
Inhibition of CTLA-4 function by the regulatory subunit of serine/threonine phosphatase 2A.
Miren L Baroja, Lalitha Vijayakrishnan, +7 authors, Vijay K Kuchroo.
J Immunol, 2002 May 08; 168(10). PMID: 11994459
Enhanced antitumor activity induced by adoptive T-cell transfer and adjunctive use of the histone deacetylase inhibitor LAQ824.
Dan D Vo, Robert M Prins, +12 authors, Antoni Ribas.
Cancer Res, 2009 Oct 29; 69(22). PMID: 19861533    Free PMC article.
Immune-checkpoint protein VISTA critically regulates the IL-23/IL-17 inflammatory axis.
Na Li, Wenwen Xu, +11 authors, Li Wang.
Sci Rep, 2017 May 05; 7(1). PMID: 28469254    Free PMC article.
TIGIT and PD-1 impair tumor antigen-specific CD8⁺ T cells in melanoma patients.
Joe-Marc Chauvin, Ornella Pagliano, +8 authors, Hassane M Zarour.
J Clin Invest, 2015 Apr 14; 125(5). PMID: 25866972    Free PMC article.
Highly Cited.
B and T lymphocyte attenuator exhibits structural and expression polymorphisms and is highly Induced in anergic CD4+ T cells.
Michelle A Hurchla, John R Sedy, +4 authors, Kenneth M Murphy.
J Immunol, 2005 Mar 08; 174(6). PMID: 15749870
CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion.
Brian Kavanagh, Shaun O'Brien, +6 authors, Lawrence Fong.
Blood, 2008 Jun 05; 112(4). PMID: 18523152    Free PMC article.
Constitutive clathrin-mediated endocytosis of CTLA-4 persists during T cell activation.
Omar S Qureshi, Satdip Kaur, +8 authors, David M Sansom.
J Biol Chem, 2012 Jan 21; 287(12). PMID: 22262842    Free PMC article.
Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients.
Laszlo G Radvanyi, Chantale Bernatchez, +32 authors, Patrick Hwu.
Clin Cancer Res, 2012 Oct 04; 18(24). PMID: 23032743    Free PMC article.
Highly Cited.
CD226 opposes TIGIT to disrupt Tregs in melanoma.
Julien Fourcade, Zhaojun Sun, +11 authors, Hassane M Zarour.
JCI Insight, 2018 Jul 27; 3(14). PMID: 30046006    Free PMC article.
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
Highly Cited.
TGFβ1-Mediated SMAD3 Enhances PD-1 Expression on Antigen-Specific T Cells in Cancer.
Benjamin V Park, Zachary T Freeman, +10 authors, Andrea L Cox.
Cancer Discov, 2016 Sep 30; 6(12). PMID: 27683557    Free PMC article.
Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity.
Rachel H McMahan, Lucy Golden-Mason, +5 authors, Hugo R Rosen.
J Clin Invest, 2010 Nov 19; 120(12). PMID: 21084749    Free PMC article.
Highly Cited.
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.
Highly Cited.
Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells.
S Liu, H Zhang, +5 authors, Z Fan.
Cell Death Differ, 2012 Nov 17; 20(3). PMID: 23154388    Free PMC article.
Genomic organization of the human LAG-3/CD4 locus.
D Bruniquel, N Borie, F Triebel.
Immunogenetics, 1997 Jan 01; 47(1). PMID: 9382927
PD-1 identifies the patient-specific CD8⁺ tumor-reactive repertoire infiltrating human tumors.
Alena Gros, Paul F Robbins, +13 authors, Steven A Rosenberg.
J Clin Invest, 2014 Mar 29; 124(5). PMID: 24667641    Free PMC article.
Highly Cited.
Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4.
P Waterhouse, J M Penninger, +6 authors, T W Mak.
Science, 1995 Nov 10; 270(5238). PMID: 7481803
Highly Cited.
Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1-CD8+ Tumor-Infiltrating T Cells.
Sema Kurtulus, Asaf Madi, +10 authors, Ana C Anderson.
Immunity, 2019 Jan 13; 50(1). PMID: 30635236    Free PMC article.
Highly Cited.
The CD28 and CTLA-4 receptors associate with the serine/threonine phosphatase PP2A.
E Chuang, T S Fisher, +7 authors, C B Thompson.
Immunity, 2000 Oct 06; 13(3). PMID: 11021529
Tyrosine phosphatase SHP-2 binding to CTLA-4: absence of direct YVKM/YFIP motif recognition.
H Schneider, C E Rudd.
Biochem Biophys Res Commun, 2000 Mar 01; 269(1). PMID: 10694513
T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition.
Enfu Hui, Jeanne Cheung, +8 authors, Ronald D Vale.
Science, 2017 Mar 11; 355(6332). PMID: 28280247    Free PMC article.
Highly Cited.
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
Highly Cited.
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.
Highly Cited.
A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC.
Kent S Boles, William Vermi, +5 authors, Marco Colonna.
Eur J Immunol, 2009 Feb 07; 39(3). PMID: 19197944    Free PMC article.
CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma.
A A Hurwitz, T F Yu, D R Leach, J P Allison.
Proc Natl Acad Sci U S A, 1998 Aug 26; 95(17). PMID: 9707601    Free PMC article.
Highly Cited.
The tyrosine phosphatase Shp2 (PTPN11) in cancer.
Gordon Chan, Demetrios Kalaitzidis, Benjamin G Neel.
Cancer Metastasis Rev, 2008 Feb 21; 27(2). PMID: 18286234
Highly Cited. Review.
The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity.
Chen Zhu, Ana C Anderson, +6 authors, Vijay K Kuchroo.
Nat Immunol, 2005 Nov 16; 6(12). PMID: 16286920
Highly Cited.
Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation.
S Read, V Malmström, F Powrie.
J Exp Med, 2000 Jul 19; 192(2). PMID: 10899916    Free PMC article.
Highly Cited.
Selective FcγR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens.
Jeremy D Waight, Dhan Chand, +14 authors, Nicholas S Wilson.
Cancer Cell, 2018 Jun 13; 33(6). PMID: 29894690    Free PMC article.
Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations.
Daniel Sanghoon Shin, Jesse M Zaretsky, +24 authors, Antoni Ribas.
Cancer Discov, 2016 Dec 03; 7(2). PMID: 27903500    Free PMC article.
Highly Cited.
A highly conserved tyrosine of Tim-3 is phosphorylated upon stimulation by its ligand galectin-9.
Philipp S van de Weyer, Michael Muehlfeit, +3 authors, E Wolfgang Kuehn.
Biochem Biophys Res Commun, 2006 Oct 31; 351(2). PMID: 17069754
Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients.
Julien Fourcade, Zhaojun Sun, +6 authors, Hassane M Zarour.
J Exp Med, 2010 Sep 08; 207(10). PMID: 20819923    Free PMC article.
Highly Cited.
Blockade of Tim-3 binding to phosphatidylserine and CEACAM1 is a shared feature of anti-Tim-3 antibodies that have functional efficacy.
Catherine A Sabatos-Peyton, James Nevin, +15 authors, Ana C Anderson.
Oncoimmunology, 2018 Jan 09; 7(2). PMID: 29308307    Free PMC article.
Upregulation of the Tim-3/galectin-9 pathway of T cell exhaustion in chronic hepatitis B virus infection.
Gaia Nebbia, Dimitra Peppa, +9 authors, Mala K Maini.
PLoS One, 2012 Nov 01; 7(10). PMID: 23112829    Free PMC article.
Highly Cited.
Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection.
Hyun-Tak Jin, Ana C Anderson, +6 authors, Rafi Ahmed.
Proc Natl Acad Sci U S A, 2010 Aug 04; 107(33). PMID: 20679213    Free PMC article.
Highly Cited.
SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.
A C Carrano, E Eytan, A Hershko, M Pagano.
Nat Cell Biol, 1999 Nov 13; 1(4). PMID: 10559916
Highly Cited.
Tumor vaccines expressing flt3 ligand synergize with ctla-4 blockade to reject preimplanted tumors.
Michael A Curran, James P Allison.
Cancer Res, 2009 Sep 10; 69(19). PMID: 19738077    Free PMC article.
Novel Effector Phenotype of Tim-3+ Regulatory T Cells Leads to Enhanced Suppressive Function in Head and Neck Cancer Patients.
Zhuqing Liu, Elizabeth L McMichael, +6 authors, Robert L Ferris.
Clin Cancer Res, 2018 May 02; 24(18). PMID: 29712685    Free PMC article.
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
M F Krummel, J P Allison.
J Exp Med, 1995 Aug 01; 182(2). PMID: 7543139    Free PMC article.
Highly Cited.
Metalloproteases regulate T-cell proliferation and effector function via LAG-3.
Nianyu Li, Yao Wang, +10 authors, Dario A A Vignali.
EMBO J, 2007 Jan 25; 26(2). PMID: 17245433    Free PMC article.
High resolution X-ray and NMR structural study of human T-cell immunoglobulin and mucin domain containing protein-3.
Amit K Gandhi, Walter M Kim, +8 authors, Richard S Blumberg.
Sci Rep, 2018 Dec 07; 8(1). PMID: 30504845    Free PMC article.
TIGIT predominantly regulates the immune response via regulatory T cells.
Sema Kurtulus, Kaori Sakuishi, +6 authors, Ana C Anderson.
J Clin Invest, 2015 Sep 29; 125(11). PMID: 26413872    Free PMC article.
Highly Cited.
Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study.
Jedd D Wolchok, Bart Neyns, +14 authors, Celeste Lebbé.
Lancet Oncol, 2009 Dec 17; 11(2). PMID: 20004617
Highly Cited.
Expression of adhesion molecules and ligands for activating and costimulatory receptors involved in cell-mediated cytotoxicity in a large panel of human melanoma cell lines.
Javier G Casado, Graham Pawelec, +6 authors, Raquel Tarazona.
Cancer Immunol Immunother, 2009 Mar 05; 58(9). PMID: 19259667
BRAF inhibition increases tumor infiltration by T cells and enhances the antitumor activity of adoptive immunotherapy in mice.
Chengwen Liu, Weiyi Peng, +18 authors, Patrick Hwu.
Clin Cancer Res, 2012 Dec 04; 19(2). PMID: 23204132    Free PMC article.
Highly Cited.
Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo.
Rituparna Das, Rakesh Verma, +8 authors, Kavita M Dhodapkar.
J Immunol, 2014 Dec 30; 194(3). PMID: 25539810    Free PMC article.
Highly Cited.
Phosphotyrosine-dependent coupling of Tim-3 to T-cell receptor signaling pathways.
Judong Lee, Ee Wern Su, +6 authors, Lawrence P Kane.
Mol Cell Biol, 2011 Aug 03; 31(19). PMID: 21807895    Free PMC article.
Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation.
G J Freeman, J G Gribben, +5 authors, L M Nadler.
Science, 1993 Nov 05; 262(5135). PMID: 7694363
Highly Cited.
Evolutionarily divergent herpesviruses modulate T cell activation by targeting the herpesvirus entry mediator cosignaling pathway.
Timothy C Cheung, Ian R Humphreys, +11 authors, Carl F Ware.
Proc Natl Acad Sci U S A, 2005 Sep 01; 102(37). PMID: 16131544    Free PMC article.
Regulation of B cell signal transduction by SH2-containing protein-tyrosine phosphatases.
K A Siminovitch, B G Neel.
Semin Immunol, 1998 Aug 08; 10(4). PMID: 9695189
Src kinases Fyn and Lck facilitate the accumulation of phosphorylated CTLA-4 and its association with PI-3 kinase in intracellular compartments of T-cells.
H Hu, C E Rudd, H Schneider.
Biochem Biophys Res Commun, 2001 Oct 26; 288(3). PMID: 11676481
Enhanced suppressor function of TIM-3+ FoxP3+ regulatory T cells.
Anne-Sophie Gautron, Margarita Dominguez-Villar, Marine de Marcken, David A Hafler.
Eur J Immunol, 2014 May 20; 44(9). PMID: 24838857    Free PMC article.
CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms.
Richard V Parry, Jens M Chemnitz, +6 authors, James L Riley.
Mol Cell Biol, 2005 Oct 18; 25(21). PMID: 16227604    Free PMC article.
Highly Cited.
PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8⁺ T cells induced by melanoma vaccines.
Julien Fourcade, Zhaojun Sun, +14 authors, Hassane M Zarour.
Cancer Res, 2013 Dec 18; 74(4). PMID: 24343228    Free PMC article.
Highly Cited.
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.
Phase I study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma.
Stephen M Ansell, Sara A Hurvitz, +10 authors, John M Timmerman.
Clin Cancer Res, 2009 Oct 08; 15(20). PMID: 19808874    Free PMC article.
Highly Cited.
Potent induction of tumor immunity by combining tumor cryoablation with anti-CTLA-4 therapy.
Rebecca Waitz, Stephen B Solomon, +4 authors, James P Allison.
Cancer Res, 2011 Nov 24; 72(2). PMID: 22108823    Free PMC article.
Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II.
Bitao Liang, Craig Workman, +10 authors, Raphael Clynes.
J Immunol, 2008 Apr 22; 180(9). PMID: 18424711
Highly Cited.
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
Identification of CD112R as a novel checkpoint for human T cells.
Yuwen Zhu, Alessandro Paniccia, +6 authors, Barish H Edil.
J Exp Med, 2016 Jan 13; 213(2). PMID: 26755705    Free PMC article.
TIM-3 Regulates CD103+ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer.
Álvaro de Mingo Pulido, Alycia Gardner, +5 authors, Brian Ruffell.
Cancer Cell, 2018 Jan 10; 33(1). PMID: 29316433    Free PMC article.
Highly Cited.
A new member of the immunoglobulin superfamily--CTLA-4.
J F Brunet, F Denizot, +4 authors, P Golstein.
Nature, 1987 Jul 16; 328(6127). PMID: 3496540
Highly Cited.
T-cell invigoration to tumour burden ratio associated with anti-PD-1 response.
Alexander C Huang, Michael A Postow, +31 authors, E John Wherry.
Nature, 2017 Apr 12; 545(7652). PMID: 28397821    Free PMC article.
Highly Cited.
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.
CTLA-4 and Autoimmunity: New Twists in the Tale.
Lucy S K Walker.
Trends Immunol, 2015 Nov 26; 36(12). PMID: 26596798    Free PMC article.
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.
Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation.
Tadashi Yokosuka, Wakana Kobayashi, +6 authors, Takashi Saito.
Immunity, 2010 Sep 28; 33(3). PMID: 20870175
BTLA interaction with HVEM expressed on CD8(+) T cells promotes survival and memory generation in response to a bacterial infection.
Marcos W Steinberg, Yujun Huang, +3 authors, Mitchell Kronenberg.
PLoS One, 2013 Nov 10; 8(10). PMID: 24205057    Free PMC article.
Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma.
John M Kirkwood, Paul Lorigan, +7 authors, Cecile A Bulanhagui.
Clin Cancer Res, 2010 Jan 21; 16(3). PMID: 20086001
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.
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.
Cellular expression and tissue distribution of the human LAG-3-encoded protein, an MHC class II ligand.
B Huard, P Gaulard, +2 authors, F Triebel.
Immunogenetics, 1994 Jan 01; 39(3). PMID: 7506235
Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy.
Se Jin Im, Masao Hashimoto, +13 authors, Rafi Ahmed.
Nature, 2016 Aug 09; 537(7620). PMID: 27501248    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.
SHP2 sails from physiology to pathology.
Mylène Tajan, Audrey de Rocca Serra, +2 authors, Armelle Yart.
Eur J Med Genet, 2015 Sep 06; 58(10). PMID: 26341048
Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2.
Tadashi Yokosuka, Masako Takamatsu, +3 authors, Takashi Saito.
J Exp Med, 2012 May 30; 209(6). PMID: 22641383    Free PMC article.
Highly Cited.
Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints.
Shohei Koyama, Esra A Akbay, +23 authors, Peter S Hammerman.
Nat Commun, 2016 Feb 18; 7. PMID: 26883990    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.
Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily.
C L Mendelsohn, E Wimmer, V R Racaniello.
Cell, 1989 Mar 10; 56(5). PMID: 2538245
Highly Cited.
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.
Anti-CTLA-4 therapy results in higher CD4+ICOShi T cell frequency and IFN-gamma levels in both nonmalignant and malignant prostate tissues.
Hong Chen, Chrysoula I Liakou, +8 authors, Padmanee Sharma.
Proc Natl Acad Sci U S A, 2009 Feb 10; 106(8). PMID: 19202079    Free PMC article.
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.
Highly Cited.
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.
PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells.
P'ng Loke, James P Allison.
Proc Natl Acad Sci U S A, 2003 Apr 17; 100(9). PMID: 12697896    Free PMC article.
Highly Cited.
PTPN11 Is a Central Node in Intrinsic and Acquired Resistance to Targeted Cancer Drugs.
Anirudh Prahallad, Guus J J E Heynen, +9 authors, Rene Bernards.
Cell Rep, 2015 Sep 15; 12(12). PMID: 26365186
Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy.
Weiyi Peng, Jie Qing Chen, +41 authors, Patrick Hwu.
Cancer Discov, 2015 Dec 10; 6(2). PMID: 26645196    Free PMC article.
Highly Cited.
Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma.
Farhad Azimi, Richard A Scolyer, +5 authors, John F Thompson.
J Clin Oncol, 2012 Jun 20; 30(21). PMID: 22711850
Highly Cited.
A molecular perspective of CTLA-4 function.
Wendy A Teft, Mark G Kirchhof, Joaquín Madrenas.
Annu Rev Immunol, 2006 Mar 23; 24. PMID: 16551244
Highly Cited. Review.
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.
Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8+ T cells in patients with melanoma.
Steven A Rosenberg, Richard M Sherry, +14 authors, Seth M Steinberg.
J Immunol, 2005 Oct 21; 175(9). PMID: 16237114
Highly Cited.
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.
Reversing T-cell Dysfunction and Exhaustion in Cancer.
Hassane M Zarour.
Clin Cancer Res, 2016 Apr 17; 22(8). PMID: 27084739    Free PMC article.
Highly Cited. Review.
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
TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression.
Xin Gao, Yibei Zhu, +7 authors, Binfeng Lu.
PLoS One, 2012 Mar 01; 7(2). PMID: 22363469    Free PMC article.
Highly Cited.
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.
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.
Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo.
Simon Read, Rebecca Greenwald, +5 authors, Fiona Powrie.
J Immunol, 2006 Sep 20; 177(7). PMID: 16982872    Free PMC article.
Highly Cited.
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.
Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement.
P S Linsley, J Bradshaw, +3 authors, R S Mittler.
Immunity, 1996 Jun 01; 4(6). PMID: 8673700
Highly Cited.
BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties.
Cara L Haymaker, Richard C Wu, +8 authors, Laszlo G Radvanyi.
Oncoimmunology, 2015 Sep 26; 4(8). PMID: 26405566    Free PMC article.
The phosphatidylserine receptors, T cell immunoglobulin mucin proteins 3 and 4, are markers of histiocytic sarcoma and other histiocytic and dendritic cell neoplasms.
David M Dorfman, Jason L Hornick, Aliakbar Shahsafaei, Gordon J Freeman.
Hum Pathol, 2010 Jul 27; 41(10). PMID: 20656318    Free PMC article.
CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients.
Chrysoula I Liakou, Ashish Kamat, +5 authors, Padmanee Sharma.
Proc Natl Acad Sci U S A, 2008 Sep 27; 105(39). PMID: 18818309    Free PMC article.
Highly Cited.
Immunization with analog peptide in combination with CpG and montanide expands tumor antigen-specific CD8+ T cells in melanoma patients.
Julien Fourcade, Pavol Kudela, +8 authors, Hassane M Zarour.
J Immunother, 2008 Sep 10; 31(8). PMID: 18779741    Free PMC article.
CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism.
P Shrikant, A Khoruts, M F Mescher.
Immunity, 1999 Nov 05; 11(4). PMID: 10549630
Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4.
T Takahashi, T Tagami, +5 authors, S Sakaguchi.
J Exp Med, 2000 Jul 19; 192(2). PMID: 10899917    Free PMC article.
Highly Cited.
Molecular basis of T cell inactivation by CTLA-4.
K M Lee, E Chuang, +7 authors, J A Bluestone.
Science, 1998 Dec 18; 282(5397). PMID: 9856951
Highly Cited.
Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity.
Stefani Spranger, Riyue Bao, Thomas F Gajewski.
Nature, 2015 May 15; 523(7559). PMID: 25970248
Highly Cited.
Attenuating lymphocyte activity: the crystal structure of the BTLA-HVEM complex.
Deanne M Compaan, Lino C Gonzalez, +3 authors, Sarah G Hymowitz.
J Biol Chem, 2005 Sep 20; 280(47). PMID: 16169851
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
Omar S Qureshi, Yong Zheng, +12 authors, David M Sansom.
Science, 2011 Apr 09; 332(6029). PMID: 21474713    Free PMC article.
Highly Cited.
Loss of IFN-γ Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy.
Jianjun Gao, Lewis Zhichang Shi, +13 authors, Padmanee Sharma.
Cell, 2016 Sep 27; 167(2). PMID: 27667683    Free PMC article.
Highly Cited.
Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma.
Jesse M Zaretsky, Angel Garcia-Diaz, +26 authors, Antoni Ribas.
N Engl J Med, 2016 Jul 20; 375(9). PMID: 27433843    Free PMC article.
Highly Cited.
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.
Highly Cited.
The CD4-related molecule, LAG-3 (CD223), regulates the expansion of activated T cells.
Creg J Workman, Dario A A Vignali.
Eur J Immunol, 2003 Apr 03; 33(4). PMID: 12672063
Phenotypic analysis of the murine CD4-related glycoprotein, CD223 (LAG-3).
Creg J Workman, Dennis S Rice, +2 authors, Dario A A Vignali.
Eur J Immunol, 2002 Sep 05; 32(8). PMID: 12209638
BTLA marks a less cytotoxic T-cell subset in diffuse large B-cell lymphoma with high expression of checkpoints.
Lina Quan, Xiuwen Lan, +5 authors, Aichun Liu.
Exp Hematol, 2018 Jan 22; 60. PMID: 29353075
Expression of lymphocyte activation gene 3 (LAG-3) on B cells is induced by T cells.
Malgorzata Kisielow, Jan Kisielow, Giuseppina Capoferri-Sollami, Klaus Karjalainen.
Eur J Immunol, 2005 Jun 23; 35(7). PMID: 15971272
A crucial role for HVEM and BTLA in preventing intestinal inflammation.
Marcos W Steinberg, Olga Turovskaya, +6 authors, Mitchell Kronenberg.
J Exp Med, 2008 Jun 04; 205(6). PMID: 18519647    Free PMC article.
Regulation of T cell receptor signaling by tyrosine phosphatase SYP association with CTLA-4.
L E Marengère, P Waterhouse, +3 authors, T W Mak.
Science, 1996 May 24; 272(5265). PMID: 8638161
Highly Cited.
Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3.
Jun Wang, Miguel F Sanmamed, +18 authors, Lieping Chen.
Cell, 2018 Dec 26; 176(1-2). PMID: 30580966    Free PMC article.
Highly Cited.
Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murine T-cell responses.
Jun Liu, Ying Yuan, +8 authors, Li Wang.
Proc Natl Acad Sci U S A, 2015 May 13; 112(21). PMID: 25964334    Free PMC article.
Highly Cited.
Fibrinogen‑like‑protein 1 promotes the invasion and metastasis of gastric cancer and is associated with poor prognosis.
Yang Zhang, Hui-Xia Qiao, +2 authors, Ju-Hui Chen.
Mol Med Rep, 2018 May 31; 18(2). PMID: 29845203    Free PMC article.
Enhancement of antitumor immunity by CTLA-4 blockade.
D R Leach, M F Krummel, J P Allison.
Science, 1996 Mar 22; 271(5256). PMID: 8596936
Highly Cited.
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.
Highly Cited.
Time to dissect the autoimmune etiology of cancer antibody immunotherapy.
Michael Dougan, Massimo Pietropaolo.
J Clin Invest, 2020 Jan 03; 130(1). PMID: 31895048    Free PMC article.
Harnessing natural killer cells for cancer immunotherapy: dispatching the first responders.
Nicholas A Maskalenko, Dmitry Zhigarev, Kerry S Campbell.
Nat Rev Drug Discov, 2022 Mar 23;. PMID: 35314852