Journal Article
. 1996 Jun; 183(6):2541-50.
doi: 10.1084/jem.183.6.2541.

CTLA-4 ligation blocks CD28-dependent T cell activation

T L Walunas 1 C Y Bakker  J A Bluestone  
  • PMID: 8676075
  •     43 References
  •     232 citations


CTLA-4 is a CD28 homologue believed to be a negative regulator of T cell function. However, the mechanism of this downregulatory activity is not well understood. The present study was designed to examine the effect of CTLA-4 ligation on cytokine production, cell survival, and cell cycle progression. The results demonstrate that the primary effect of CTLA-4 ligation is not the induction of apoptosis. Instead, CTLA-4 signaling blocks IL-2 production, IL-2 receptor expression, and cell cycle progression of activated T cells. Moreover, the effect of CTLA-4 signaling was manifested after initial T cell activation. Inhibition of IL-2 receptor expression and cell cycle progression was more pronounced at late (72 h) time points after initial activation. The effects of anti-CTLA-4 mAbs were most apparent in the presence of optimal CD28-mediated costimulation consistent with the finding that CTLA-4 upregulation was CD28-dependent. Finally, the addition of exogenous IL-2 to the cultures restored IL-2 receptor expression and T cell proliferation. These results suggest that CTLA-4 signaling does not regulate cell survival or responsiveness to IL-2, but does inhibit CD28-dependent IL-2 production.

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J Immunol, 2005 Nov 23; 175(11). PMID: 16301685    Free PMC article.
Lack of intrinsic CTLA-4 expression has minimal effect on regulation of antiviral T-cell immunity.
Dirk Homann, Wolfgang Dummer, +4 authors, Matthias G von Herrath.
J Virol, 2005 Dec 15; 80(1). PMID: 16352552    Free PMC article.
Co-expression of sCD40LIg and CTLA4Ig mediated by adenovirus prolonged mouse skin allograft survival.
Zhao-lun Li, Pu-xun Tian, Wu-jun Xue, Jun Wu.
J Zhejiang Univ Sci B, 2006 May 13; 7(6). PMID: 16691637    Free PMC article.
Intrapatient dose escalation of anti-CTLA-4 antibody in patients with metastatic melanoma.
Ajay V Maker, James C Yang, +11 authors, Steven A Rosenberg.
J Immunother, 2006 Jun 27; 29(4). PMID: 16799341    Free PMC article.
Inhibition of T cell activation and autoimmune diabetes using a B cell surface-linked CTLA-4 agonist.
Brian T Fife, Matthew D Griffin, +2 authors, Jeffrey A Bluestone.
J Clin Invest, 2006 Aug 04; 116(8). PMID: 16886063    Free PMC article.
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.
Cancer immunosuppression and autoimmune disease: beyond immunosuppressive networks for tumour immunity.
Ryungsa Kim, Manabu Emi, Kazuaki Tanabe.
Immunology, 2006 Sep 29; 119(2). PMID: 17005005    Free PMC article.
Inhibiting costimulatory activation of T cells : a viable treatment option for rheumatoid arthritis?
Louise C Pollard.
Drugs, 2007 Jan 11; 67(1). PMID: 17209660
The CTLA-4 -1661A/G and -1772T/C dimorphisms in Japanese patients with systemic sclerosis.
Fujio Takeuchi, Naoko Nakaue, +3 authors, Kiyoaki Tanimoto.
Rheumatol Int, 2007 Jan 18; 27(8). PMID: 17225925
CTLA-4 regulates allergen response by modulating GATA-3 protein level per cell.
Francesca Nasta, Silvia Corinti, +3 authors, Claudio Pioli.
Immunology, 2007 Feb 23; 121(1). PMID: 17313444    Free PMC article.
Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade.
Stephanie G Downey, Jacob A Klapper, +12 authors, Steven A Rosenberg.
Clin Cancer Res, 2007 Nov 06; 13(22 Pt 1). PMID: 17982122    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.
CTLA-4 is a direct target of Wnt/beta-catenin signaling and is expressed in human melanoma tumors.
Kavita V Shah, Andy J Chien, Cassian Yee, Randall T Moon.
J Invest Dermatol, 2008 Jun 20; 128(12). PMID: 18563180    Free PMC article.
Primary biliary cirrhosis is associated with a genetic variant in the 3' flanking region of the CTLA4 gene.
Brian D Juran, Elizabeth J Atkinson, +2 authors, Konstantinos N Lazaridis.
Gastroenterology, 2008 Sep 10; 135(4). PMID: 18778710    Free PMC article.
CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit.
Jianda Yuan, Sacha Gnjatic, +17 authors, Jedd D Wolchok.
Proc Natl Acad Sci U S A, 2008 Dec 17; 105(51). PMID: 19074257    Free PMC article.
Highly Cited.
CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance.
Randall H Friedline, David S Brown, +7 authors, Cynthia A Chambers.
J Exp Med, 2009 Feb 04; 206(2). PMID: 19188497    Free PMC article.
Highly Cited.
Cholesterol depletion associated with Leishmania major infection alters macrophage CD40 signalosome composition and effector function.
Abdur Rub, Ranadhir Dey, +5 authors, Bhaskar Saha.
Nat Immunol, 2009 Feb 10; 10(3). PMID: 19198591
Enhanced selection of FoxP3+ T-regulatory cells protects CTLA-4-deficient mice from CNS autoimmune disease.
Johan Verhagen, Leona Gabrysová, +4 authors, David C Wraith.
Proc Natl Acad Sci U S A, 2009 Feb 17; 106(9). PMID: 19218450    Free PMC article.
[A novel treatment option in rheumatoid arthritis: abatacept, a selective modulator of T-cell co-stimulation].
Christian Dejaco, Christina Duftner, Edith Wipfler, Michael Schirmer.
Wien Med Wochenschr, 2009 Feb 28; 159(3-4). PMID: 19247593
Memory T cells need CD28 costimulation to remember.
Alina C Boesteanu, Peter D Katsikis.
Semin Immunol, 2009 Mar 10; 21(2). PMID: 19268606    Free PMC article.
Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells.
Hélène Bour-Jordan, Jeffrey A Bluestone.
Immunol Rev, 2009 May 12; 229(1). PMID: 19426214    Free PMC article.
CD152 (CTLA-4) determines CD4 T cell migration in vitro and in vivo.
Karin Knieke, Holger Hoff, +5 authors, Monika C Brunner-Weinzierl.
PLoS One, 2009 May 30; 4(5). PMID: 19479036    Free PMC article.
Anti-CTLA-4 treatment induces IL-10-producing ICOS+ regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis.
C Coquerelle, G Oldenhove, +6 authors, M Moser.
Gut, 2009 Jun 10; 58(10). PMID: 19505881    Free PMC article.
Association of cytotoxic T lymphocyte antigen-4 gene polymorphisms and HLA class II alleles with the development of type 1 diabetes in Korean children and adolescents.
Min Ho Jung, Jeesuk Yu, +3 authors, Byung Churl Lee.
J Korean Med Sci, 2009 Dec 02; 24(6). PMID: 19949652    Free PMC article.
Association of CTLA4 gene polymorphism in Iranian patients with ankylosing spondylitis.
Esfandiar Azizi, Ahmad Massoud, +6 authors, Mohammad Hossein Nicknam.
J Clin Immunol, 2009 Dec 17; 30(2). PMID: 20012554
CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms.
Wataru Ise, Masako Kohyama, +5 authors, Kenneth M Murphy.
Nat Immunol, 2009 Dec 29; 11(2). PMID: 20037585    Free PMC article.
Correlation of clinical and immunological data in a metastatic melanoma patient with heterogeneous tumor responses to ipilimumab therapy.
Jianda Yuan, David B Page, +14 authors, Jedd D Wolchok.
Cancer Immun, 2010 Jan 08; 10. PMID: 20052966    Free PMC article.
Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival.
Geoffrey Y Ku, Jianda Yuan, +7 authors, Jedd D Wolchok.
Cancer, 2010 Feb 10; 116(7). PMID: 20143434    Free PMC article.
Highly Cited.
Role of CTLA-4, IL-18 and IL-10 on the Induction of Low Dose Oral Tolerance.
Kathleen Siobhan Barone, Rachael Burns, +3 authors, Tifany Nolan.
J Ky Acad Sci, 2008 Mar 01; 69(1). PMID: 20200594    Free PMC article.
B7 family molecules as regulators of the maternal immune system in pregnancy.
Margaret G Petroff, Antoine Perchellet.
Am J Reprod Immunol, 2010 Apr 14; 63(6). PMID: 20384620    Free PMC article.
HIV-1 impairs in vitro priming of naïve T cells and gives rise to contact-dependent suppressor T cells.
Karlhans F Che, Rachel L Sabado, +5 authors, Marie Larsson.
Eur J Immunol, 2010 May 11; 40(8). PMID: 20455275    Free PMC article.
Carriage of a tumor necrosis factor polymorphism amplifies the cytotoxic T-lymphocyte antigen 4 attributed risk of primary biliary cirrhosis: evidence for a gene-gene interaction.
Brian D Juran, Elizabeth J Atkinson, +6 authors, Konstantinos N Lazaridis.
Hepatology, 2010 Jun 26; 52(1). PMID: 20578265    Free PMC article.
Highly specialized role of Forkhead box O transcription factors in the immune system.
Anne S Dejean, Stephen M Hedrick, Yann M Kerdiles.
Antioxid Redox Signal, 2010 Aug 03; 14(4). PMID: 20673126    Free PMC article.
A novel clinically relevant strategy to abrogate autoimmunity and regulate alloimmunity in NOD mice.
Andrea Vergani, Francesca D'Addio, +17 authors, Paolo Fiorina.
Diabetes, 2010 Sep 02; 59(9). PMID: 20805386    Free PMC article.
Mechanism of cellular rejection in transplantation.
Elizabeth Ingulli.
Pediatr Nephrol, 2010 Jan 01; 25(1). PMID: 21476231    Free PMC article.
Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family.
Hélène Bour-Jordan, Jonathan H Esensten, +3 authors, Jeffrey A Bluestone.
Immunol Rev, 2011 Apr 15; 241(1). PMID: 21488898    Free PMC article.
Highly Cited. Review.
The soluble CTLA-4 splice variant protects from type 1 diabetes and potentiates regulatory T-cell function.
Kay D Gerold, Peilin Zheng, +3 authors, Stephan Kissler.
Diabetes, 2011 May 24; 60(7). PMID: 21602513    Free PMC article.
Regulatory T cell: a protection for tumour cells.
Yi Wang, Yushui Ma, +4 authors, Xizhong Shen.
J Cell Mol Med, 2011 Sep 08; 16(3). PMID: 21895966    Free PMC article.
Toxoplasma gondii induces B7-2 expression through activation of JNK signal transduction.
Pedro Morgado, Yi-Ching Ong, John C Boothroyd, Melissa B Lodoen.
Infect Immun, 2011 Sep 14; 79(11). PMID: 21911468    Free PMC article.
CTLA-4 gene polymorphism and the risk of systemic lupus erythematosus in the Chinese population.
Ahmad Taha Khalaf, Ji-Quan Song, +2 authors, Tie-Chi Lei.
J Biomed Biotechnol, 2011 Sep 15; 2011. PMID: 21915163    Free PMC article.
The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses.
Lucy S K Walker, David M Sansom.
Nat Rev Immunol, 2011 Nov 26; 11(12). PMID: 22116087
Highly Cited.
CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma.
Peter A Prieto, James C Yang, +6 authors, Giao Q Phan.
Clin Cancer Res, 2012 Jan 25; 18(7). PMID: 22271879    Free PMC article.
Highly Cited.
Ligation of cytotoxic T lymphocyte antigen-4 to T cell receptor inhibits T cell activation and directs differentiation into Foxp3+ regulatory T cells.
Jozsef Karman, Ji-Lei Jiang, +7 authors, Yunxiang Zhu.
J Biol Chem, 2012 Feb 18; 287(14). PMID: 22337882    Free PMC article.
Regulation generation: the suppressive functions of human regulatory T cells.
Wendy A Goodman, Kevin D Cooper, Thomas S McCormick.
Crit Rev Immunol, 2012 Mar 21; 32(1). PMID: 22428855    Free PMC article.
The role of coinhibitory signaling pathways in transplantation and tolerance.
Martina M McGrath, Nader Najafian.
Front Immunol, 2012 May 09; 3. PMID: 22566929    Free PMC article.
Molecular mechanisms of treg-mediated T cell suppression.
Angelika Schmidt, Nina Oberle, Peter H Krammer.
Front Immunol, 2012 May 09; 3. PMID: 22566933    Free PMC article.
Highly Cited.
The genetic basis of graves' disease.
Rafał Płoski, Konrad Szymański, Tomasz Bednarczuk.
Curr Genomics, 2012 Jun 02; 12(8). PMID: 22654555    Free PMC article.
Cutting edge: cell-extrinsic immune regulation by CTLA-4 expressed on conventional T cells.
Chun Jing Wang, Rupert Kenefeck, +6 authors, Lucy S K Walker.
J Immunol, 2012 Jul 04; 189(3). PMID: 22753931    Free PMC article.
The role of costimulatory molecules in directing the functional differentiation of alloreactive T helper cells.
C N Magee, O Boenisch, N Najafian.
Am J Transplant, 2012 Jul 05; 12(10). PMID: 22759274    Free PMC article.
Ipilimumab pharmacotherapy in patients with metastatic melanoma.
Joanne M Jeter, Lee D Cranmer, Evan M Hersh.
Clin Med Insights Oncol, 2012 Aug 21; 6. PMID: 22904648    Free PMC article.
Transient deficiency of dendritic cells results in lack of a merozoite surface protein 1-specific CD4 T cell response during peak Plasmodium chabaudi blood-stage infection.
Anne-Marit Sponaas, Nikolai Belyaev, +2 authors, Jean Langhorne.
Infect Immun, 2012 Sep 26; 80(12). PMID: 23006847    Free PMC article.
Immunotherapies: the blockade of inhibitory signals.
Yan-Ling Wu, Jing Liang, +2 authors, Hiroshi Sugiyama.
Int J Biol Sci, 2012 Dec 01; 8(10). PMID: 23197939    Free PMC article.
Brief report: increased expression of a short splice variant of CTLA-4 exacerbates lupus in MRL/lpr mice.
Kunihiro Ichinose, Zheng Zhang, +6 authors, George C Tsokos.
Arthritis Rheum, 2012 Dec 04; 65(3). PMID: 23203389    Free PMC article.
Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor-specific cytotoxic T lymphocytes.
Yoshiki Shigematsu, Takeshi Hanagiri, +8 authors, Fumihiro Tanaka.
Oncol Lett, 2012 Dec 04; 4(4). PMID: 23205074    Free PMC article.
Immune tolerance and transplantation.
Onder Alpdogan, Marcel R M van den Brink.
Semin Oncol, 2012 Dec 05; 39(6). PMID: 23206840    Free PMC article.
Association of the CTLA-4 +49A/G polymorphism with rheumatoid arthritis in Chinese Han population.
Ming-Jie Tang, Zu-Bin Zhou.
Mol Biol Rep, 2012 Dec 25; 40(3). PMID: 23264071
The B7-independent isoform of CTLA-4 functions to regulate autoimmune diabetes.
Melanie Stumpf, Xuyu Zhou, Jeffrey A Bluestone.
J Immunol, 2013 Jan 08; 190(3). PMID: 23293354    Free PMC article.
Abnormal T regulatory cells (Tregs: FOXP3+, CTLA-4+), myeloid-derived suppressor cells (MDSCs: monocytic, granulocytic) and polarised T helper cell profiles (Th1, Th2, Th17) in women with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC) and surgery: failure of abolition of abnormal treg profile with treatment and correlation of treg levels with pathological response to NAC.
Chandan Verma, Jennifer M Eremin, +5 authors, Oleg Eremin.
J Transl Med, 2013 Jan 17; 11. PMID: 23320561    Free PMC article.
Immunomodulatory therapy for melanoma: ipilimumab and beyond.
Margaret K Callahan, Michael A Postow, Jedd D Wolchok.
Clin Dermatol, 2013 Feb 27; 31(2). PMID: 23438382    Free PMC article.
The nature of activatory and tolerogenic dendritic cell-derived signal II.
Ghaith Bakdash, Simone P Sittig, +2 authors, I Jolanda M de Vries.
Front Immunol, 2013 Mar 02; 4. PMID: 23450201    Free PMC article.
Modulation of tumor immunity by soluble and membrane-bound molecules at the immunological synapse.
Pablo A González, Leandro J Carreño, +3 authors, Alexis M Kalergis.
Clin Dev Immunol, 2013 Mar 28; 2013. PMID: 23533456    Free PMC article.
At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy.
Andrew M Intlekofer, Craig B Thompson.
J Leukoc Biol, 2013 Apr 30; 94(1). PMID: 23625198    Free PMC article.
Highly Cited. Review.
A bispecific protein capable of engaging CTLA-4 and MHCII protects non-obese diabetic mice from autoimmune diabetes.
Hongmei Zhao, Jozsef Karman, +8 authors, Yunxiang Zhu.
PLoS One, 2013 May 25; 8(5). PMID: 23704916    Free PMC article.
Treg and CTLA-4: two intertwining pathways to immune tolerance.
Lucy S K Walker.
J Autoimmun, 2013 Jul 16; 45. PMID: 23849743    Free PMC article.
Highly Cited. Review.
Use of ipilimumab in the treatment of melanoma.
Utkarsh H Acharya, Joanne M Jeter.
Clin Pharmacol, 2013 Oct 12; 5(Suppl 1). PMID: 24113540    Free PMC article.
Clinical Implications of Co-Inhibitory Molecule Expression in the Tumor Microenvironment for DC Vaccination: A Game of Stop and Go.
Angela Vasaturo, Stefania Di Blasio, +4 authors, Stanleyson V Hato.
Front Immunol, 2013 Dec 19; 4. PMID: 24348481    Free PMC article.
Common variants on cytotoxic T lymphocyte antigen-4 polymorphisms contributes to type 1 diabetes susceptibility: evidence based on 58 studies.
Jingnan Wang, Lianyong Liu, +3 authors, Mingjun Gu.
PLoS One, 2014 Jan 28; 9(1). PMID: 24465825    Free PMC article.
Fusion protein of mutant B7-DC and Fc enhances the antitumor immune effect of GM-CSF-secreting whole-cell vaccine.
Masatsugu Kojima, Satoshi Murata, +3 authors, Tohru Tani.
J Immunother, 2014 Mar 07; 37(3). PMID: 24598447    Free PMC article.
Tyrosine 201 of the cytoplasmic tail of CTLA-4 critically affects T regulatory cell suppressive function.
Melanie Stumpf, Xuyu Zhou, Shunsuke Chikuma, Jeffrey A Bluestone.
Eur J Immunol, 2014 Mar 22; 44(6). PMID: 24648182    Free PMC article.
Clinical Benefit from Ipilimumab Therapy in Melanoma Patients may be Associated with Serum CTLA4 Levels.
Anna M Leung, Agnes Fermin Lee, +8 authors, Delphine J Lee.
Front Oncol, 2014 Jun 07; 4. PMID: 24904825    Free PMC article.
Humanized mice as a model for aberrant responses in human T cell immunotherapy.
Nalini K Vudattu, Frank Waldron-Lynch, +6 authors, Kevan C Herold.
J Immunol, 2014 Jun 20; 193(2). PMID: 24943216    Free PMC article.
The novel immunotherapeutic molecule T11TS modulates glioma-induced changes of key components of the immunological synapse in favor of T cell activation and glioma abrogation.
Suhnrita Chaudhuri, Manoj Kumar Singh, +9 authors, Swapna Chaudhuri.
J Neurooncol, 2014 Jul 17; 120(1). PMID: 25026997
T Helper Cells Fate Mapping by Co-stimulatory Molecules and its Functions in Allograft Rejection and Tolerance.
R Abdoli, N Najafian.
Int J Organ Transplant Med, 2014 Sep 04; 5(3). PMID: 25184030    Free PMC article.
Braking bad: novel mechanisms of CTLA-4 inhibition of T cell responses.
S M Krummey, M L Ford.
Am J Transplant, 2014 Nov 13; 14(12). PMID: 25387592    Free PMC article.
The coinhibitory receptor CTLA-4 controls B cell responses by modulating T follicular helper, T follicular regulatory, and T regulatory cells.
Peter T Sage, Alison M Paterson, Scott B Lovitch, Arlene H Sharpe.
Immunity, 2014 Dec 20; 41(6). PMID: 25526313    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.
A transendocytosis model of CTLA-4 function predicts its suppressive behavior on regulatory T cells.
Tie Zheng Hou, Omar S Qureshi, +4 authors, David M Sansom.
J Immunol, 2015 Jan 30; 194(5). PMID: 25632005    Free PMC article.
Association of the CTLA-4 1722TC polymorphism and systemic lupus erythematosus: a systematic review and meta analysis.
Mahdieh Shojaa, Mehrdad Aghaie, +7 authors, Shima RoknSharifi.
Med J Islam Repub Iran, 2015 Feb 20; 28. PMID: 25694990    Free PMC article.
T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance.
B Ye, X Liu, +3 authors, Y Chen.
Cell Death Dis, 2015 Mar 20; 6. PMID: 25789969    Free PMC article.
Highly Cited. Review.
IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer.
K Abiko, N Matsumura, +7 authors, M Mandai.
Br J Cancer, 2015 Apr 14; 112(9). PMID: 25867264    Free PMC article.
Highly Cited.
Checkpoint modulation--A new way to direct the immune system against renal cell carcinoma.
Jens Bedke, Stephan Kruck, +2 authors, Peter J Goebell.
Hum Vaccin Immunother, 2015 Apr 29; 11(5). PMID: 25912622    Free PMC article.
Podocyte directed therapy of nephrotic syndrome-can we bring the inside out?
Janina Müller-Deile, Mario Schiffer.
Pediatr Nephrol, 2015 May 06; 31(3). PMID: 25939817
In-situ tumor vaccination: Bringing the fight to the tumor.
Robert H Pierce, Jean S Campbell, +2 authors, Holbrook E K Kohrt.
Hum Vaccin Immunother, 2015 Jun 10; 11(8). PMID: 26055074    Free PMC article.
Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity.
Alison M Paterson, Scott B Lovitch, +9 authors, Arlene H Sharpe.
J Exp Med, 2015 Sep 16; 212(10). PMID: 26371185    Free PMC article.
Highly Cited.
Patients with chronic lymphocytic leukaemia (CLL) differ in the pattern of CTLA-4 expression on CLL cells: the possible implications for immunotherapy with CTLA-4 blocking antibody.
Lidia Ciszak, Irena Frydecka, +2 authors, Agata Kosmaczewska.
Tumour Biol, 2015 Oct 23; 37(3). PMID: 26490985    Free PMC article.
The Role of Alternative Splicing in the Control of Immune Homeostasis and Cellular Differentiation.
Mehmet Yabas, Hannah Elliott, Gerard F Hoyne.
Int J Mol Sci, 2015 Dec 26; 17(1). PMID: 26703587    Free PMC article.
Induction of CD4(+) Regulatory and Polarized Effector/helper T Cells by Dendritic Cells.
Manfred B Lutz.
Immune Netw, 2016 Mar 05; 16(1). PMID: 26937228    Free PMC article.
Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family.
Frank A Schildberg, Sarah R Klein, Gordon J Freeman, Arlene H Sharpe.
Immunity, 2016 May 19; 44(5). PMID: 27192563    Free PMC article.
Highly Cited. Review.
Immune Checkpoint Inhibitors: Review and Management of Endocrine Adverse Events.
Elisa González-Rodríguez, Delvys Rodríguez-Abreu, Spanish Group for Cancer Immuno-Biotherapy (GETICA).
Oncologist, 2016 Jun 17; 21(7). PMID: 27306911    Free PMC article.
Highly Cited. Review.
Immune Mechanisms in Myelodysplastic Syndrome.
Andreas Glenthøj, Andreas Due Ørskov, +3 authors, Kirsten Grønbæk.
Int J Mol Sci, 2016 Jun 18; 17(6). PMID: 27314337    Free PMC article.
Metastatic melanoma and immunotherapy.
Benjamin Herzberg, David E Fisher.
Clin Immunol, 2016 Jul 20; 172. PMID: 27430520    Free PMC article.
The clinical impact of ICOS signal in colorectal cancer patients.
Yan Zhang, Yang Luo, +4 authors, Ming Zhong.
Oncoimmunology, 2016 Jul 29; 5(5). PMID: 27467961    Free PMC article.
Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.
Benjamin Herzberg, Meghan J Campo, Justin F Gainor.
Oncologist, 2016 Aug 19; 22(1). PMID: 27534574    Free PMC article.
Crucial Contributions by T Lymphocytes (Effector, Regulatory, and Checkpoint Inhibitor) and Cytokines (TH1, TH2, and TH17) to a Pathological Complete Response Induced by Neoadjuvant Chemotherapy in Women with Breast Cancer.
Viriya Kaewkangsadan, Chandan Verma, +3 authors, Oleg Eremin.
J Immunol Res, 2016 Oct 26; 2016. PMID: 27777963    Free PMC article.
Diacylglycerol Kinases (DGKs): Novel Targets for Improving T Cell Activity in Cancer.
Matthew J Riese, Edmund K Moon, Bryon D Johnson, Steven M Albelda.
Front Cell Dev Biol, 2016 Nov 02; 4. PMID: 27800476    Free PMC article.
PD-1-PD-L1 immune-checkpoint blockade in B-cell lymphomas.
Aaron Goodman, Sandip P Patel, Razelle Kurzrock.
Nat Rev Clin Oncol, 2016 Nov 03; 14(4). PMID: 27805626
Highly Cited. Review.
Unraveling the Role of Allo-Antibodies and Transplant Injury.
Yoshiko Matsuda, Minnie M Sarwal.
Front Immunol, 2016 Nov 08; 7. PMID: 27818660    Free PMC article.
Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility.
Monica Marzagalli, Marina Montagnani Marelli, +3 authors, Patrizia Limonta.
Front Endocrinol (Lausanne), 2016 Nov 12; 7. PMID: 27833586    Free PMC article.
Immunoregulation in Fungal Diseases.
Jonathan A Roussey, Michal A Olszewski, John J Osterholzer.
Microorganisms, 2016 Dec 16; 4(4). PMID: 27973396    Free PMC article.
The prognostic value of cytotoxic T-lymphocyte antigen 4 in cancers: a systematic review and meta-analysis.
Pingping Hu, Qiqi Liu, +4 authors, Jiandong Zhang.
Sci Rep, 2017 Feb 18; 7. PMID: 28211499    Free PMC article.
Systematic Review.
State of the art in anti-cancer mAbs.
S M Chiavenna, J P Jaworski, A Vendrell.
J Biomed Sci, 2017 Feb 22; 24(1). PMID: 28219375    Free PMC article.
In Situ Activation of Pituitary-Infiltrating T Lymphocytes in Autoimmune Hypophysitis.
Han-Huei Lin, Angelika Gutenberg, +7 authors, Shey-Cherng Tzou.
Sci Rep, 2017 Mar 07; 7. PMID: 28262761    Free PMC article.
Mechanistic and pharmacologic insights on immune checkpoint inhibitors.
Randy F Sweis, Jason J Luke.
Pharmacol Res, 2017 Mar 23; 120. PMID: 28323141    Free PMC article.
The double-edged sword of (re)expression of genes by hypomethylating agents: from viral mimicry to exploitation as priming agents for targeted immune checkpoint modulation.
Florian Wolff, Michael Leisch, +2 authors, Lisa Pleyer.
Cell Commun Signal, 2017 Apr 01; 15(1). PMID: 28359286    Free PMC article.
Immunometabolic Regulations Mediated by Coinhibitory Receptors and Their Impact on T Cell Immune Responses.
Nikolaos Patsoukis, Jessica D Weaver, +3 authors, Vassiliki A Boussiotis.
Front Immunol, 2017 Apr 27; 8. PMID: 28443090    Free PMC article.
Podocytes from the diagnostic and therapeutic point of view.
Janina Müller-Deile, Mario Schiffer.
Pflugers Arch, 2017 May 17; 469(7-8). PMID: 28508947
Make immunological peace not war: Potential applications of tolerogenic dendritic cells.
Emma Louise Walton.
Biomed J, 2017 May 20; 40(2). PMID: 28521904    Free PMC article.
Harnessing the properties of dendritic cells in the pursuit of immunological tolerance.
Christopher Horton, Kumaran Shanmugarajah, Paul J Fairchild.
Biomed J, 2017 May 20; 40(2). PMID: 28521905    Free PMC article.
Challenges and opportunities in targeting the CD28/CTLA-4 pathway in transplantation and autoimmunity.
Rebecca L Crepeau, Mandy L Ford.
Expert Opin Biol Ther, 2017 May 21; 17(8). PMID: 28525959    Free PMC article.
The promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approaches.
Panagiota Economopoulou, Ioannis Kotsantis, Amanda Psyrri.
ESMO Open, 2017 Aug 30; 1(6). PMID: 28848660    Free PMC article.
Clinical Applications of Immunotherapy Combination Methods and New Opportunities for the Future.
Ece Esin.
Biomed Res Int, 2017 Aug 30; 2017. PMID: 28848761    Free PMC article.
Metabolic strategies of melanoma cells: Mechanisms, interactions with the tumor microenvironment, and therapeutic implications.
Grant M Fischer, Y N Vashisht Gopal, +3 authors, Michael A Davies.
Pigment Cell Melanoma Res, 2017 Oct 20; 31(1). PMID: 29049843    Free PMC article.
Selective CD28 blockade attenuates CTLA-4-dependent CD8+ memory T cell effector function and prolongs graft survival.
Danya Liu, I Raul Badell, Mandy L Ford.
JCI Insight, 2018 Jan 13; 3(1). PMID: 29321374    Free PMC article.
Functions of NKG2D in CD8+ T cells: an opportunity for immunotherapy.
Kushal Prajapati, Cynthia Perez, +2 authors, Jose A Guevara-Patino.
Cell Mol Immunol, 2018 Feb 06; 15(5). PMID: 29400704    Free PMC article.
Gastrointestinal toxicity of immune checkpoint inhibitors: from mechanisms to management.
Mark A Samaan, Polychronis Pavlidis, +2 authors, Peter M Irving.
Nat Rev Gastroenterol Hepatol, 2018 Mar 08; 15(4). PMID: 29512649
The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation.
Lidia Karabon, Miroslaw Markiewicz, +6 authors, Irena Frydecka.
J Immunol Res, 2018 Mar 27; 2018. PMID: 29577049    Free PMC article.
Regulatory Role of CD4+ T Cells in Myocarditis.
Daria Vdovenko, Urs Eriksson.
J Immunol Res, 2018 Jul 24; 2018. PMID: 30035131    Free PMC article.
Description of CD8+ Regulatory T Lymphocytes and Their Specific Intervention in Graft-versus-Host and Infectious Diseases, Autoimmunity, and Cancer.
Martha R Vieyra-Lobato, Jorge Vela-Ojeda, +2 authors, Martha C Moreno-Lafont.
J Immunol Res, 2018 Aug 30; 2018. PMID: 30155493    Free PMC article.
Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints.
Lee-Shing Chang, Romualdo Barroso-Sousa, +3 authors, Le Min.
Endocr Rev, 2018 Sep 06; 40(1). PMID: 30184160    Free PMC article.
Serum sCTLA-4 levels and clinical manifestations in ankylosing spondylitis patients.
Sultan Pınar Çetintepe, Taşkın Şentürk, Gökhan Sargın, Neriman Aydın.
Eur J Rheumatol, 2018 Sep 07; 5(2). PMID: 30185360    Free PMC article.
New advances in immunotherapy for non-small cell lung cancer.
Haifeng Qin, Fang Wang, +4 authors, Hongjun Gao.
Am J Transl Res, 2018 Sep 14; 10(8). PMID: 30210667    Free PMC article.
The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy.
Jiawen Qian, Chen Wang, +7 authors, Yiwei Chu.
J Neuroinflammation, 2018 Oct 20; 15(1). PMID: 30333036    Free PMC article.
[Mode of action, new targets and potential biomarkers in modern immunotherapy].
J Bedke, V Stühler, T Todenhöfer, A Stenzl.
Urologe A, 2018 Oct 24; 57(11). PMID: 30350128
Immune Checkpoint Inhibition in Hodgkin Lymphoma.
Ryan H Moy, Anas Younes.
Hemasphere, 2018 Feb 16; 2(1). PMID: 31723749    Free PMC article.
Impact of infection on transplantation tolerance.
Shuangjin Yu, Chang Su, Xunrong Luo.
Immunol Rev, 2019 Sep 21; 292(1). PMID: 31538351    Free PMC article.
Immunotherapy Is Changing First-Line Treatment of Metastatic Renal-Cell Carcinoma.
Matthew K Labriola, Kristen A Batich, +5 authors, Tian Zhang.
Clin Genitourin Cancer, 2019 Mar 13; 17(3). PMID: 30858035    Free PMC article.
Natural and Induced Tolerogenic Dendritic Cells.
Courtney A Iberg, Daniel Hawiger.
J Immunol, 2020 Feb 06; 204(4). PMID: 32015076    Free PMC article.
Restoring self-tolerance in autoimmune diseases by enhancing regulatory T-cells.
Prabhakaran Kumar, Shikha Saini, +2 authors, Bellur S Prabhakar.
Cell Immunol, 2018 Nov 30; 339. PMID: 30482489    Free PMC article.
Impact of selective CD28 blockade on virus-specific immunity to a murine Epstein-Barr virus homolog.
Rebecca L Crepeau, Joseph A Elengickal, Glenn M La Muraglia, Mandy L Ford.
Am J Transplant, 2019 Feb 26; 19(8). PMID: 30801917    Free PMC article.
Regulatory T cells limit unconventional memory to preserve the capacity to mount protective CD8 memory responses to pathogens.
Andreia S Da Costa, Jessica B Graham, Jessica L Swarts, Jennifer M Lund.
Proc Natl Acad Sci U S A, 2019 May 01; 116(20). PMID: 31036644    Free PMC article.
Engineered Dendritic Cell-Directed Concurrent Activation of Multiple T cell Inhibitory Pathways Induces Robust Immune Tolerance.
Radhika R Gudi, Subha Karumuthil-Melethil, +2 authors, Chenthamarakshan Vasu.
Sci Rep, 2019 Aug 21; 9(1). PMID: 31427630    Free PMC article.
Checkpoint blockade inhibitors enhances the effectiveness of a Listeria monocytogenes-based melanoma vaccine.
Ryan P Gilley, Peter H Dube.
Oncotarget, 2020 Mar 07; 11(7). PMID: 32133048    Free PMC article.
Advances in immunotherapy delivery from implantable and injectable biomaterials.
David G Leach, Simon Young, Jeffrey D Hartgerink.
Acta Biomater, 2019 Feb 17; 88. PMID: 30771535    Free PMC article.
Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges.
Kei Kunimasa, Taichiro Goto.
Int J Mol Sci, 2020 Jan 23; 21(2). PMID: 31963413    Free PMC article.
Workup and Management of Immune-Mediated Colitis in Patients Treated with Immune Checkpoint Inhibitors.
Bhavana Pendurthi Singh, John L Marshall, Aiwu Ruth He.
Oncologist, 2020 Mar 13; 25(3). PMID: 32162824    Free PMC article.
CD28-Dependent CTLA-4 Expression Fine-Tunes the Activation of Human Th17 Cells.
Scott M Krummey, Christina R Hartigan, Danya Liu, Mandy L Ford.
iScience, 2020 Mar 24; 23(4). PMID: 32203908    Free PMC article.
Development of immune checkpoint therapy for cancer.
Jill M Fritz, Michael J Lenardo.
J Exp Med, 2019 May 10; 216(6). PMID: 31068379    Free PMC article.
Highly Cited. Review.
Immune-Related Adverse Events: Pneumonitis.
Linda Zhong, Mehmet Altan, Vickie R Shannon, Ajay Sheshadri.
Adv Exp Med Biol, 2020 Apr 18; 1244. PMID: 32301020    Free PMC article.
Soluble CD80 Protein Delays Tumor Growth and Promotes Tumor-Infiltrating Lymphocytes.
Lucas A Horn, Tiha M Long, +2 authors, Suzanne Ostrand-Rosenberg.
Cancer Immunol Res, 2017 Nov 11; 6(1). PMID: 29122838    Free PMC article.
Inhibitory checkpoints in human natural killer cells: IUPHAR Review 28.
F R Mariotti, L Quatrini, +5 authors, L Moretta.
Br J Pharmacol, 2020 Apr 27; 177(13). PMID: 32335915    Free PMC article.
Antisense targeting of CD47 enhances human cytotoxic T-cell activity and increases survival of mice bearing B16 melanoma when combined with anti-CTLA4 and tumor irradiation.
Anthony L Schwartz, Pulak R Nath, +7 authors, David D Roberts.
Cancer Immunol Immunother, 2019 Oct 20; 68(11). PMID: 31628526    Free PMC article.
Fungal infection risks associated with the use of cytokine antagonists and immune checkpoint inhibitors.
Xin Li, Susanna Kp Lau, Patrick Cy Woo.
Exp Biol Med (Maywood), 2020 Jul 10; 245(13). PMID: 32640893    Free PMC article.
Epigenetic Mechanisms of Resistance to Immune Checkpoint Inhibitors.
Alexandre Perrier, Audrey Didelot, +2 authors, Simon Garinet.
Biomolecules, 2020 Jul 28; 10(7). PMID: 32708698    Free PMC article.
Cytokines, Chemokines, and Other Biomarkers of Response for Checkpoint Inhibitor Therapy in Skin Cancer.
Jennifer A Bridge, James C Lee, +2 authors, Jeffrey A Bluestone.
Front Med (Lausanne), 2019 Jan 12; 5. PMID: 30631766    Free PMC article.
Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma.
Andreas Kahlmeyer, Christine G Stöhr, +5 authors, Franziska Erlmeier.
J Clin Med, 2019 May 30; 8(5). PMID: 31137694    Free PMC article.
A Model for Apoptotic-Cell-Mediated Adaptive Immune Evasion via CD80-CTLA-4 Signaling.
Abraam M Yakoub, Stefan Schülke.
Front Pharmacol, 2019 Jun 20; 10. PMID: 31214024    Free PMC article.
Current Clinical Applications and Future Perspectives of Immune Checkpoint Inhibitors in Non-Hodgkin Lymphoma.
John Apostolidis, Ayman Sayyed, +2 authors, Hani Al Hashmi.
J Immunol Res, 2020 Nov 13; 2020. PMID: 33178841    Free PMC article.
Genetic and molecular origins of colorectal Cancer among the Iranians: an update.
Mohammad Reza Abbaszadegan, Meysam Moghbeli.
Diagn Pathol, 2018 Dec 24; 13(1). PMID: 30579343    Free PMC article.
Association of CTLA-4 tagging polymorphisms and haplotypes with hepatocellular carcinoma risk: A case-control study.
Jing Yang, Jiaochun Liu, +4 authors, Jianping Chen.
Medicine (Baltimore), 2019 Jul 25; 98(29). PMID: 31335675    Free PMC article.
The Multifaceted Role of Th1, Th9, and Th17 Cells in Immune Checkpoint Inhibition Therapy.
Jongdae Lee, Beatriz Lozano-Ruiz, +3 authors, Jose M González-Navajas.
Front Immunol, 2021 Mar 30; 12. PMID: 33777008    Free PMC article.
Fundamentals of T Cell Metabolism and Strategies to Enhance Cancer Immunotherapy.
Guillermo O Rangel Rivera, Hannah M Knochelmann, +5 authors, Chrystal M Paulos.
Front Immunol, 2021 Apr 06; 12. PMID: 33815400    Free PMC article.
Natural Killer Cells and Regulatory T Cells Cross Talk in Hepatocellular Carcinoma: Exploring Therapeutic Options for the Next Decade.
Amber G Bozward, Frazer Warricker, Ye H Oo, Salim I Khakoo.
Front Immunol, 2021 May 18; 12. PMID: 33995362    Free PMC article.
Soluble cytotoxic T-lymphocyte-associated antigen 4 (sCTLA-4) as a potential biomarker for diagnosis and evaluation of the prognosis in Glioma.
Jiajia Liu, Xiaoyi Tian, +2 authors, Wenqi Song.
BMC Immunol, 2021 May 20; 22(1). PMID: 34006227    Free PMC article.
Immune Checkpoint Inhibition for Triple-Negative Breast Cancer: Current Landscape and Future Perspectives.
Huimei Yi, Ying Li, +3 authors, Xiyun Deng.
Front Oncol, 2021 Jun 08; 11. PMID: 34094935    Free PMC article.
DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy.
Ruixue Huang, Ping-Kun Zhou.
Signal Transduct Target Ther, 2021 Jul 10; 6(1). PMID: 34238917    Free PMC article.
Immune PET Imaging.
Osigbemhe Iyalomhe, Michael D Farwell.
Radiol Clin North Am, 2021 Aug 17; 59(5). PMID: 34392924    Free PMC article.
Antitumor activity of the third generation EphA2 CAR-T cells against glioblastoma is associated with interferon gamma induced PD-L1.
Zhijing An, Yi Hu, +6 authors, Xiaosong Zhong.
Oncoimmunology, 2021 Aug 20; 10(1). PMID: 34408922    Free PMC article.
TIGIT regulates apoptosis of risky memory T cell subsets implicated in belatacept-resistant rejection.
He Sun, Christina R Hartigan, +6 authors, Mandy L Ford.
Am J Transplant, 2021 Mar 24; 21(10). PMID: 33756063    Free PMC article.
Cytotoxic T lymphocyte antigen-4 regulates development of xenogenic graft versus host disease in mice via modulation of host immune responses induced by changes in human T cell engraftment and gene expression.
Chunxu Gao, Debra Gardner, +7 authors, Ravi Malaviya.
Clin Exp Immunol, 2021 Sep 07; 206(3). PMID: 34487545    Free PMC article.
Pulmonary Toxicities of Immunotherapy.
Mehmet Altan, Linda Zhong, Vickie R Shannon, Ajay Sheshadri.
Adv Exp Med Biol, 2022 Jan 02; 1342. PMID: 34972974
Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier.
Somayeh Vafaei, Angelina O Zekiy, +4 authors, Majid Zamani.
Cancer Cell Int, 2022 Jan 05; 22(1). PMID: 34980128    Free PMC article.
Tumor Immunology and Immunotherapy of Non-Small-Cell Lung Cancer.
Tina Cascone, Jared Fradette, Monika Pradhan, Don L Gibbons.
Cold Spring Harb Perspect Med, 2021 Sep 29; 12(5). PMID: 34580079    Free PMC article.
Addressing the Elephant in the Immunotherapy Room: Effector T-Cell Priming versus Depletion of Regulatory T-Cells by Anti-CTLA-4 Therapy.
Megan M Y Hong, Saman Maleki Vareki.
Cancers (Basel), 2022 Mar 26; 14(6). PMID: 35326731    Free PMC article.
Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.
Adel Naimi, Rebar N Mohammed, +11 authors, Ehsan Razeghian.
Cell Commun Signal, 2022 Apr 09; 20(1). PMID: 35392976    Free PMC article.
Computational analysis of hot spots and binding mechanism in the PD-1/PD-L1 interaction.
Dading Huang, Wei Wen, +2 authors, John Z H Zhang.
RSC Adv, 2019 May 14; 9(26). PMID: 35516311    Free PMC article.
The Single-Cell Level Perspective of the Tumor Microenvironment and Its Remodeling by CAR-T Cells.
Sanxing Gao, Ryohichi Sugimura.
Cancer Treat Res, 2022 May 14; 183. PMID: 35551664