. 2021 Jan; 26(4):951-967.
doi: 10.1016/j.drudis.2021.01.002.

Tumor-infiltrating CD8+ T cell antitumor efficacy and exhaustion: molecular insights

Sandeep Kumar 1 Sunil Kumar Singh 2 Basabi Rana 3 Ajay Rana 3 
  • PMID: 33450394
  •     207 References
  •     4 citations


Host immunity has an essential role in the clinical management of cancers. Therefore, it is advantageous to choose therapies that can promote tumor cell death and concurrently boost host immunity. The dynamic tumor microenvironment (TME) determines whether an antineoplastic drug will elicit favorable or disparaging immune responses from tumor-infiltrating lymphocytes (TILs). CD8+ T cells are one of the primary tumor-infiltrating immune cells that deliver antitumor responses. Here, we review the influence of various factors in the TME on CD8+ T cell exhaustion and survival, and possible strategies for restoring CD8+ T cell effector function through immunotherapy.

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Karen Silence, Torsten Dreier, +9 authors, Hans J De Haard.
MAbs, 2014 Feb 05; 6(2). PMID: 24492296    Free PMC article.
Breaking through the central tolerance ceiling to unleash anticancer immune responses.
Maureen A Su, Mark S Anderson.
Oncoimmunology, 2015 Jan 23; 3(8). PMID: 25610739    Free PMC article.
Molecular Programming of Tumor-Infiltrating CD8+ T Cells and IL15 Resistance.
Andrew L Doedens, Mark P Rubinstein, +6 authors, Ananda W Goldrath.
Cancer Immunol Res, 2016 Aug 04; 4(9). PMID: 27485135    Free PMC article.
A novel antibody-TCR (AbTCR) platform combines Fab-based antigen recognition with gamma/delta-TCR signaling to facilitate T-cell cytotoxicity with low cytokine release.
Yiyang Xu, Zhiyuan Yang, +11 authors, Cheng Liu.
Cell Discov, 2018 Nov 28; 4. PMID: 30479831    Free PMC article.
Toll-like receptor agonists in cancer therapy.
Sylvia Adams.
Immunotherapy, 2010 Jun 22; 1(6). PMID: 20563267    Free PMC article.
Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer.
Shinichi Kageyama, Hiroaki Ikeda, +20 authors, Hiroshi Shiku.
Clin Cancer Res, 2015 Apr 10; 21(10). PMID: 25855804
VISTA expressed in tumour cells regulates T cell function.
Kumuluzi Mulati, Junzo Hamanishi, +14 authors, Masaki Mandai.
Br J Cancer, 2018 Nov 02; 120(1). PMID: 30382166    Free PMC article.
First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas.
Ajay K Gopal, Ronald Levy, +13 authors, Nancy L Bartlett.
Clin Cancer Res, 2020 Mar 08; 26(11). PMID: 32144134
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.
The p38 MAPK inhibitor BIRB796 enhances the antitumor effects of VX680 in cervical cancer.
Xin Jin, Qingqing Mo, +7 authors, Pingbo Chen.
Cancer Biol Ther, 2016 Apr 16; 17(5). PMID: 27082306    Free PMC article.
Modulation of p38 MAPK signaling enhances dendritic cell activation of human CD4+ Th17 responses to ovarian tumor antigen.
Martin J Cannon, Hannah E Goyne, +4 authors, Maurizio Chiriva-Internati.
Cancer Immunol Immunother, 2013 Jan 29; 62(5). PMID: 23354626    Free PMC article.
TGFβ Blockade Augments PD-1 Inhibition to Promote T-Cell-Mediated Regression of Pancreatic Cancer.
Daniel R Principe, Alex Park, +8 authors, Ajay Rana.
Mol Cancer Ther, 2018 Dec 28; 18(3). PMID: 30587556    Free PMC article.
Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8+ T cells.
Beatris Mastelic-Gavillet, Blanca Navarro Rodrigo, +23 authors, Selena Vigano.
J Immunother Cancer, 2019 Oct 12; 7(1). PMID: 31601268    Free PMC article.
Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in mice.
Ying Wang, Lijing Su, +17 authors, Bruce Beutler.
Proc Natl Acad Sci U S A, 2018 Aug 29; 115(37). PMID: 30150374    Free PMC article.
Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy.
Daniel R Principe, Matthew Narbutis, +12 authors, Ajay Rana.
Cancer Res, 2020 Apr 03; 80(15). PMID: 32238357    Free PMC article.
Chromatin states define tumour-specific T cell dysfunction and reprogramming.
Mary Philip, Lauren Fairchild, +11 authors, Andrea Schietinger.
Nature, 2017 May 18; 545(7655). PMID: 28514453    Free PMC article.
Highly Cited.
Mutational activation of the epidermal growth factor receptor down-regulates major histocompatibility complex class I expression via the extracellular signal-regulated kinase in non-small cell lung cancer.
Satomi Watanabe, Hidetoshi Hayashi, +10 authors, Kazuhiko Nakagawa.
Cancer Sci, 2018 Nov 06; 110(1). PMID: 30390416    Free PMC article.
Urelumab alone or in combination with rituximab in patients with relapsed or refractory B-cell lymphoma.
John Timmerman, Charles Herbaux, +17 authors, Ronald Levy.
Am J Hematol, 2020 Feb 14; 95(5). PMID: 32052473    Free PMC article.
New PD-L1 inhibitors in non-small cell lung cancer - impact of atezolizumab.
Nagashree Seetharamu, Isabel R Preeshagul, Kevin M Sullivan.
Lung Cancer (Auckl), 2017 Aug 02; 8. PMID: 28761384    Free PMC article.
Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors.
Jaikumar Duraiswamy, Karen M Kaluza, Gordon J Freeman, George Coukos.
Cancer Res, 2013 May 02; 73(12). PMID: 23633484    Free PMC article.
Highly Cited.
Mixed lineage kinase-3/JNK1 axis promotes migration of human gastric cancer cells following gastrin stimulation.
Prajna Mishra, Subramanian Senthivinayagam, +2 authors, Basabi Rana.
Mol Endocrinol, 2010 Feb 13; 24(3). PMID: 20150185    Free PMC article.
CD96 Is an Immune Checkpoint That Regulates CD8+ T-cell Antitumor Function.
Deepak Mittal, Ailin Lepletier, +16 authors, Mark J Smyth.
Cancer Immunol Res, 2019 Mar 22; 7(4). PMID: 30894377    Free PMC article.
PD-1 blockade in subprimed CD8 cells induces dysfunctional PD-1+CD38hi cells and anti-PD-1 resistance.
Vivek Verma, Rajeev K Shrimali, +25 authors, Samir N Khleif.
Nat Immunol, 2019 Jul 31; 20(9). PMID: 31358999    Free PMC article.
Highly Cited.
Targeting Tumors with IL-10 Prevents Dendritic Cell-Mediated CD8+ T Cell Apoptosis.
Jian Qiao, Zhida Liu, +10 authors, Yang-Xin Fu.
Cancer Cell, 2019 Jun 12; 35(6). PMID: 31185213
An intra-tumoral niche maintains and differentiates stem-like CD8 T cells.
Caroline S Jansen, Nataliya Prokhnevska, +26 authors, Haydn Kissick.
Nature, 2019 Dec 13; 576(7787). PMID: 31827286    Free PMC article.
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Rationalized inhibition of mixed lineage kinase 3 and CD70 enhances life span and antitumor efficacy of CD8+ T cells.
Sandeep Kumar, Sunil Kumar Singh, +9 authors, Ajay Rana.
J Immunother Cancer, 2020 Aug 08; 8(2). PMID: 32759234    Free PMC article.
ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity.
Mario Martínez Soldevilla, Helena Villanueva, +10 authors, Fernando Pastor.
Mol Ther, 2019 Aug 14; 27(11). PMID: 31405808    Free PMC article.
A preclinical evaluation of aminopyridines as putative therapeutic agents in the treatment of botulism.
L L Simpson.
Infect Immun, 1986 Jun 01; 52(3). PMID: 3011675    Free PMC article.
Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers.
Oliver M T Pearce, Robin M Delaine-Smith, +22 authors, Frances R Balkwill.
Cancer Discov, 2017 Dec 03; 8(3). PMID: 29196464    Free PMC article.
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A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity.
Marta Compte, Seandean Lykke Harwood, +19 authors, Luis Alvarez-Vallina.
Nat Commun, 2018 Nov 18; 9(1). PMID: 30442944    Free PMC article.
Highly Cited.
PTEN Loss Promotes Intratumoral Androgen Synthesis and Tumor Microenvironment Remodeling via Aberrant Activation of RUNX2 in Castration-Resistant Prostate Cancer.
Yinhui Yang, Yang Bai, +13 authors, Wanhai Xu.
Clin Cancer Res, 2017 Nov 24; 24(4). PMID: 29167276    Free PMC article.
Direct interaction between CD155 and CD96 promotes immunosuppression in lung adenocarcinoma.
Hui Zhang, Qianwen Liu, +8 authors, Zunfu Ke.
Cell Mol Immunol, 2020 Sep 13; 18(6). PMID: 32917981    Free PMC article.
Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma.
Peter J Siska, Kathryn E Beckermann, +15 authors, Jeffrey C Rathmell.
JCI Insight, 2017 Jun 15; 2(12). PMID: 28614802    Free PMC article.
Highly Cited.
Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy.
Daniel Baumann, Tanja Hägele, +12 authors, Rienk Offringa.
Nat Commun, 2020 May 03; 11(1). PMID: 32358491    Free PMC article.
Blockade of PDGFRβ circumvents resistance to MEK-JAK inhibition via intratumoral CD8+ T-cells infiltration in triple-negative breast cancer.
Murugan Kalimutho, Debottam Sinha, +7 authors, Kum Kum Khanna.
J Exp Clin Cancer Res, 2019 Feb 20; 38(1). PMID: 30777101    Free PMC article.
Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapy.
Daniel Shae, Kyle W Becker, +8 authors, John T Wilson.
Nat Nanotechnol, 2019 Jan 22; 14(3). PMID: 30664751    Free PMC article.
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Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA.
Jiaxi Wu, Lijun Sun, +4 authors, Zhijian J Chen.
Science, 2012 Dec 22; 339(6121). PMID: 23258412    Free PMC article.
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Evolution of melanoma cross-resistance to CD8+ T cells and MAPK inhibition in the course of BRAFi treatment.
Natalia Pieper, Anne Zaremba, +15 authors, Fang Zhao.
Oncoimmunology, 2018 Sep 18; 7(8). PMID: 30221038    Free PMC article.
Distinct tumor immune microenvironments in primary and metastatic lesions in gastric cancer patients.
Seung-Myoung Son, Chang Gok Woo, +12 authors, Hye Sook Han.
Sci Rep, 2020 Sep 02; 10(1). PMID: 32868848    Free PMC article.
A guide to cancer immunotherapy: from T cell basic science to clinical practice.
Alex D Waldman, Jill M Fritz, Michael J Lenardo.
Nat Rev Immunol, 2020 May 21; 20(11). PMID: 32433532    Free PMC article.
Lenalidomide induces degradation of IKZF1 and IKZF3.
Jan Krönke, Slater N Hurst, Benjamin L Ebert.
Oncoimmunology, 2015 Jan 23; 3(7). PMID: 25610725    Free PMC article.
The TLR-7 agonist, imiquimod, enhances dendritic cell survival and promotes tumor antigen-specific T cell priming: relation to central nervous system antitumor immunity.
Robert M Prins, Noah Craft, +5 authors, Linda M Liau.
J Immunol, 2005 Dec 21; 176(1). PMID: 16365406
Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer.
Sahar M A Mahmoud, Emma Claire Paish, +5 authors, Andrew R Green.
J Clin Oncol, 2011 Apr 13; 29(15). PMID: 21483002
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Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+ T cells.
Shu Wang, Jose Campos, +5 authors, Cristiana Guiducci.
Proc Natl Acad Sci U S A, 2016 Nov 02; 113(46). PMID: 27799536    Free PMC article.
Highly Cited.
Hypoxia-Induced VISTA Promotes the Suppressive Function of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment.
Jie Deng, Jiannan Li, +12 authors, Rodwell Mabaera.
Cancer Immunol Res, 2019 May 16; 7(7). PMID: 31088847    Free PMC article.
Highly Cited.
Activation of human CD141+ and CD1c+ dendritic cells in vivo with combined TLR3 and TLR7/8 ligation.
Frances E Pearson, Karshing Chang, +5 authors, Kristen J Radford.
Immunol Cell Biol, 2018 Jan 19; 96(4). PMID: 29344995
Efficacy of adoptive therapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis.
U Dafni, O Michielin, +15 authors, G Coukos.
Ann Oncol, 2019 Oct 01; 30(12). PMID: 31566658
Systematic Review.
Combination cancer immunotherapy targeting PD-1 and GITR can rescue CD8.
Bei Wang, Wen Zhang, +21 authors, Dimitris Skokos.
Sci Immunol, 2018 Nov 06; 3(29). PMID: 30389797
Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape.
Seng-Ryong Woo, Meghan E Turnis, +18 authors, Dario A A Vignali.
Cancer Res, 2011 Dec 22; 72(4). PMID: 22186141    Free PMC article.
Highly Cited.
Molecular mechanisms of T-cell tolerance.
Roza I Nurieva, Xindong Liu, Chen Dong.
Immunol Rev, 2011 Apr 15; 241(1). PMID: 21488895    Free PMC article.
Carboplatin chemoresistance is associated with CD11b+/Ly6C+ myeloid release and upregulation of TIGIT and LAG3/CD160 exhausted T cells.
Doxakis Anestakis, Savvas Petanidis, +3 authors, Theodora Katopodi.
Mol Immunol, 2019 Dec 22; 118. PMID: 31862674
Dual TLR agonist nanodiscs as a strong adjuvant system for vaccines and immunotherapy.
Rui Kuai, Xiaoqi Sun, +8 authors, James J Moon.
J Control Release, 2018 Apr 28; 282. PMID: 29702142    Free PMC article.
Expanding the Therapeutic Window for CAR T Cell Therapy in Solid Tumors: The Knowns and Unknowns of CAR T Cell Biology.
Keisuke Watanabe, Shunichiro Kuramitsu, Avery D Posey, Carl H June.
Front Immunol, 2018 Nov 13; 9. PMID: 30416506    Free PMC article.
Highly Cited. Review.
MAP4K4 negatively regulates CD8 T cell-mediated antitumor and antiviral immunity.
Emel Esen, Ismail Sergin, +11 authors, Weilan Ye.
Sci Immunol, 2020 Mar 30; 5(45). PMID: 32220977
Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact.
Takuya Komura, Yoshio Sakai, +8 authors, Shuichi Kaneko.
Cancer Sci, 2015 Apr 02; 106(6). PMID: 25827621    Free PMC article.
Oncology meets immunology: the cancer-immunity cycle.
Daniel S Chen, Ira Mellman.
Immunity, 2013 Jul 31; 39(1). PMID: 23890059
Highly Cited. Review.
T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses.
Alireza Saeidi, Keivan Zandi, +7 authors, Esaki Muthu Shankar.
Front Immunol, 2018 Nov 27; 9. PMID: 30473697    Free PMC article.
Highly Cited. Review.
PARP Inhibitor Efficacy Depends on CD8+ T-cell Recruitment via Intratumoral STING Pathway Activation in BRCA-Deficient Models of Triple-Negative Breast Cancer.
Constantia Pantelidou, Olmo Sonzogni, +14 authors, Geoffrey I Shapiro.
Cancer Discov, 2019 Apr 25; 9(6). PMID: 31015319    Free PMC article.
Highly Cited.
Mutated nucleophosmin 1 as immunotherapy target in acute myeloid leukemia.
Dyantha I van der Lee, Rogier M Reijmers, +13 authors, Marieke Griffioen.
J Clin Invest, 2019 Jan 15; 129(2). PMID: 30640174    Free PMC article.
Highly Cited.
Discovery of Small Molecules for the Reversal of T Cell Exhaustion.
Brett S Marro, Jaroslav Zak, +3 authors, Michael B A Oldstone.
Cell Rep, 2019 Dec 05; 29(10). PMID: 31801090    Free PMC article.
TLR agonists: our best frenemy in cancer immunotherapy.
Sabina Kaczanowska, Ann Mary Joseph, Eduardo Davila.
J Leukoc Biol, 2013 Mar 12; 93(6). PMID: 23475577    Free PMC article.
Highly Cited. Review.
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.
Acetate Promotes T Cell Effector Function during Glucose Restriction.
Jing Qiu, Matteo Villa, +22 authors, Erika L Pearce.
Cell Rep, 2019 May 16; 27(7). PMID: 31091446    Free PMC article.
Highly Cited.
Immunogenicity of pembrolizumab in patients with advanced tumors.
Marianne J H van Vugt, Julie A Stone, +12 authors, Tomoko Freshwater.
J Immunother Cancer, 2019 Aug 10; 7(1). PMID: 31395089    Free PMC article.
T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer.
Kyung Do Byun, Hyo Jun Hwang, +5 authors, Jin Sook Jeong.
J Breast Cancer, 2019 Jan 05; 21(4). PMID: 30607162    Free PMC article.
PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer.
Qiongshu Li, Muyun Liu, +11 authors, Weibin Liu.
Oncol Lett, 2018 Mar 21; 15(4). PMID: 29556312    Free PMC article.
Tim-3 expression represents dysfunctional tumor infiltrating T cells in renal cell carcinoma.
Chen Cai, Yi-Fan Xu, +6 authors, Yinghao Sun.
World J Urol, 2015 Aug 09; 34(4). PMID: 26253654
Preclinical development of T-cell receptor-engineered T-cell therapy targeting the 5T4 tumor antigen on renal cell carcinoma.
Yuexin Xu, Alicia J Morales, +4 authors, Scott S Tykodi.
Cancer Immunol Immunother, 2019 Nov 07; 68(12). PMID: 31686124    Free PMC article.
Elements of cancer immunity and the cancer-immune set point.
Daniel S Chen, Ira Mellman.
Nature, 2017 Jan 20; 541(7637). PMID: 28102259
Highly Cited. Review.
Phenotype molding of stromal cells in the lung tumor microenvironment.
Diether Lambrechts, Els Wauters, +15 authors, Bernard Thienpont.
Nat Med, 2018 Jul 11; 24(8). PMID: 29988129
Highly Cited.
A Phase II Study of Tumor-infiltrating Lymphocyte Therapy for Human Papillomavirus-associated Epithelial Cancers.
Sanja Stevanović, Sarah R Helman, +10 authors, Christian S Hinrichs.
Clin Cancer Res, 2018 Dec 07; 25(5). PMID: 30518633    Free PMC article.
Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations.
Judith A Seidel, Atsushi Otsuka, Kenji Kabashima.
Front Oncol, 2018 Apr 13; 8. PMID: 29644214    Free PMC article.
Highly Cited. Review.
Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti-CTLA-4 antibody.
Danbee Ha, Atsushi Tanaka, +10 authors, Shimon Sakaguchi.
Proc Natl Acad Sci U S A, 2018 Dec 28; 116(2). PMID: 30587582    Free PMC article.
Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma.
Aras Toker, Linh T Nguyen, +14 authors, Pamela S Ohashi.
Clin Cancer Res, 2018 Aug 02; 24(22). PMID: 30065096
Tumor-infiltrating regulatory dendritic cells inhibit CD8+ T cell function via L-arginine metabolism.
Lyse A Norian, Paulo C Rodriguez, +4 authors, Paul M Allen.
Cancer Res, 2009 Mar 19; 69(7). PMID: 19293186    Free PMC article.
Highly Cited.
CD137 accurately identifies and enriches for naturally occurring tumor-reactive T cells in tumor.
Qunrui Ye, De-Gang Song, +5 authors, Daniel J Powell.
Clin Cancer Res, 2013 Sep 21; 20(1). PMID: 24045181    Free PMC article.
Highly Cited.
STING activation reprograms tumor vasculatures and synergizes with VEGFR2 blockade.
Hannah Yang, Won Suk Lee, +7 authors, Chan Kim.
J Clin Invest, 2019 Jul 26; 129(10). PMID: 31343989    Free PMC article.
IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses.
Rosa M Santana Carrero, Figen Beceren-Braun, +6 authors, Kimberly S Schluns.
Proc Natl Acad Sci U S A, 2018 Dec 28; 116(2). PMID: 30587590    Free PMC article.
Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance.
Douglas C Palmer, Geoffrey C Guittard, +17 authors, Nicholas P Restifo.
J Exp Med, 2015 Nov 04; 212(12). PMID: 26527801    Free PMC article.
Intratumoral immunotherapy with TLR7/8 agonist MEDI9197 modulates the tumor microenvironment leading to enhanced activity when combined with other immunotherapies.
Stefanie R Mullins, John P Vasilakos, +16 authors, Robert W Wilkinson.
J Immunother Cancer, 2019 Sep 13; 7(1). PMID: 31511088    Free PMC article.
An agonistic anti-Toll-like receptor 4 monoclonal antibody as an effective adjuvant for cancer immunotherapy.
Hiroki Tsukamoto, Kanae Kubota, +5 authors, Yoshihisa Tomioka.
Immunology, 2019 Sep 14; 158(2). PMID: 31515801    Free PMC article.
Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8+ T-cell axis.
Craig M Brackett, Bojidar Kojouharov, +5 authors, Andrei V Gudkov.
Proc Natl Acad Sci U S A, 2016 Feb 03; 113(7). PMID: 26831100    Free PMC article.
PD-1 blockade augments humoral immunity through ICOS-mediated CD4+ T cell instruction.
Meiyu Zhang, Liliang Xia, +8 authors, Ying Wang.
Int Immunopharmacol, 2018 Nov 19; 66. PMID: 30448635
LKB1 loss promotes endometrial cancer progression via CCL2-dependent macrophage recruitment.
Christopher G Peña, Yuji Nakada, +10 authors, Diego H Castrillon.
J Clin Invest, 2015 Sep 29; 125(11). PMID: 26413869    Free PMC article.
Adaptive plasticity of IL-10+ and IL-35+ Treg cells cooperatively promotes tumor T cell exhaustion.
Deepali V Sawant, Hiroshi Yano, +16 authors, Dario A A Vignali.
Nat Immunol, 2019 Apr 03; 20(6). PMID: 30936494    Free PMC article.
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.
Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells.
Stefani Spranger, Robbert M Spaapen, +4 authors, Thomas F Gajewski.
Sci Transl Med, 2013 Aug 30; 5(200). PMID: 23986400    Free PMC article.
Highly Cited.
STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling.
Hiroki Ishikawa, Glen N Barber.
Nature, 2008 Aug 30; 455(7213). PMID: 18724357    Free PMC article.
Highly Cited.
The coordination of T-cell function by serine/threonine kinases.
David Finlay, Doreen Cantrell.
Cold Spring Harb Perspect Biol, 2011 Mar 23; 3(1). PMID: 21421912    Free PMC article.
Sorafenib-resistant hepatocellular carcinoma stratified by phosphorylated ERK activates PD-1 immune checkpoint.
Jiang Chen, Tong Ji, +11 authors, Xiujun Cai.
Oncotarget, 2016 Apr 30; 7(27). PMID: 27129180    Free PMC article.
Combination anti-CTLA-4 plus anti-PD-1 checkpoint blockade utilizes cellular mechanisms partially distinct from monotherapies.
Spencer C Wei, Nana-Ama A S Anang, +8 authors, James P Allison.
Proc Natl Acad Sci U S A, 2019 Oct 23; 116(45). PMID: 31636208    Free PMC article.
Tumor masses support naive T cell infiltration, activation, and differentiation into effectors.
Elizabeth D Thompson, Hilda L Enriquez, Yang-Xin Fu, Victor H Engelhard.
J Exp Med, 2010 Jul 28; 207(8). PMID: 20660615    Free PMC article.
OX40 (CD134) and OX40 ligand, important immune checkpoints in cancer.
Juan Deng, Sha Zhao, +4 authors, Yayi He.
Onco Targets Ther, 2019 Oct 01; 12. PMID: 31564917    Free PMC article.
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.
TIGIT Expression Is Associated with T-cell Suppression and Exhaustion and Predicts Clinical Outcome and Anti-PD-1 Response in Follicular Lymphoma.
Zhi-Zhang Yang, Hyo Jin Kim, +6 authors, Stephen M Ansell.
Clin Cancer Res, 2020 Jul 08; 26(19). PMID: 32631956
Negative Co-stimulation Constrains T Cell Differentiation by Imposing Boundaries on Possible Cell States.
Spencer C Wei, Roshan Sharma, +8 authors, James P Allison.
Immunity, 2019 Mar 31; 50(4). PMID: 30926234    Free PMC article.
Developing neoantigen-targeted T cell-based treatments for solid tumors.
Tori N Yamamoto, Rigel J Kishton, Nicholas P Restifo.
Nat Med, 2019 Oct 09; 25(10). PMID: 31591590
Highly Cited. Review.
GTPase-activating protein Rasal1 associates with ZAP-70 of the TCR and negatively regulates T-cell tumor immunity.
Youg Raj Thaker, Monika Raab, Klaus Strebhardt, Christopher E Rudd.
Nat Commun, 2019 Oct 24; 10(1). PMID: 31641113    Free PMC article.
Impact of chemotactic factors and receptors on the cancer immune infiltrate: a bioinformatics study revealing homogeneity and heterogeneity among patient cohorts.
Gautier Stoll, Jonathan Pol, +2 authors, Guido Kroemer.
Oncoimmunology, 2018 Oct 06; 7(10). PMID: 30288345    Free PMC article.
In situ vaccination with defined factors overcomes T cell exhaustion in distant tumors.
Danny N Khalil, Nathan Suek, +18 authors, Taha Merghoub.
J Clin Invest, 2019 Jul 23; 129(8). PMID: 31329159    Free PMC article.
Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells.
Qian Chen, Quanyin Hu, +7 authors, Zhen Gu.
Adv Mater, 2019 Mar 28; 31(23). PMID: 30916367    Free PMC article.
Highly Cited.
Reinforce the antitumor activity of CD8+ T cells via glutamine restriction.
Shogo Nabe, Takeshi Yamada, +7 authors, Masakatsu Yamashita.
Cancer Sci, 2018 Oct 12; 109(12). PMID: 30302856    Free PMC article.
STAT3 inhibition enhances CDN-induced STING signaling and antitumor immunity.
Jianwen Pei, Yibo Zhang, +5 authors, Junmin Quan.
Cancer Lett, 2019 Feb 23; 450. PMID: 30790684
Enhancing CD8+ T Cell Fatty Acid Catabolism within a Metabolically Challenging Tumor Microenvironment Increases the Efficacy of Melanoma Immunotherapy.
Ying Zhang, Raj Kurupati, +17 authors, Hildegund C J Ertl.
Cancer Cell, 2017 Sep 13; 32(3). PMID: 28898698    Free PMC article.
Highly Cited.
The Future of Cancer Diagnosis, Treatment and Surveillance: A Systemic Review on Immunotherapy and Immuno-PET Radiotracers.
Virginia Liberini, Riccardo Laudicella, +5 authors, Désirée Deandreis.
Molecules, 2021 May 01; 26(8). PMID: 33920423    Free PMC article.
Systematic Review.
The Importance of Metabolism for Immune Homeostasis in Allergic Diseases.
Juan Rodriguez-Coira, Alma Villaseñor, +5 authors, Domingo Barber.
Front Immunol, 2021 Aug 17; 12. PMID: 34394086    Free PMC article.
The Key Gene Expression Patterns and Prognostic Factors in Malignant Transformation from Enchondroma to Chondrosarcoma.
Junqing Wu, Yue Huang, +8 authors, He Huang.
Front Oncol, 2021 Sep 28; 11. PMID: 34568022    Free PMC article.
A deep learning quantified stroma-immune score to predict survival of patients with stage II-III colorectal cancer.
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