. 2021 Jul; 11:641428.
doi: 10.3389/fonc.2021.641428.

The Tumor Microenvironment Factors That Promote Resistance to Immune Checkpoint Blockade Therapy

Bonnie L Russell 1 Selisha A Sooklal 1 Sibusiso T Malindisa 1 Lembelani Jonathan Daka 2 Monde Ntwasa 1 
  • PMID: 34268109
  •     184 References
  •     5 citations


Through genetic and epigenetic alterations, cancer cells present the immune system with a diversity of antigens or neoantigens, which the organism must distinguish from self. The immune system responds to neoantigens by activating naïve T cells, which mount an anticancer cytotoxic response. T cell activation begins when the T cell receptor (TCR) interacts with the antigen, which is displayed by the major histocompatibility complex (MHC) on antigen-presenting cells (APCs). Subsequently, accessory stimulatory or inhibitory molecules transduce a secondary signal in concert with the TCR/antigen mediated stimulus. These molecules serve to modulate the activation signal's strength at the immune synapse. Therefore, the activation signal's optimum amplitude is maintained by a balance between the costimulatory and inhibitory signals. This system comprises the so-called immune checkpoints such as the programmed cell death (PD-1) and Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and is crucial for the maintenance of self-tolerance. Cancers often evade the intrinsic anti-tumor activity present in normal physiology primarily by the downregulation of T cell activation. The blockade of the immune checkpoint inhibitors using specific monoclonal antibodies has emerged as a potentially powerful anticancer therapy strategy. Several drugs have been approved mainly for solid tumors. However, it has emerged that there are innate and acquired mechanisms by which resistance is developed against these therapies. Some of these are tumor-intrinsic mechanisms, while others are tumor-extrinsic whereby the microenvironment may have innate or acquired resistance to checkpoint inhibitors. This review article will examine mechanisms by which resistance is mounted against immune checkpoint inhibitors focussing on anti-CTL4-A and anti-PD-1/PD-Ll since drugs targeting these checkpoints are the most developed.

Keywords: CTLA-4; Immune checkpoint inhibitor; PD-1; resistance; tumor microenvironment.

Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC.
Mark A Socinski, Robert M Jotte, +18 authors, IMpower150 Study Group.
N Engl J Med, 2018 Jun 05; 378(24). PMID: 29863955
Highly Cited.
O Warburg, F Wind, E Negelein.
J Gen Physiol, 1927 Mar 07; 8(6). PMID: 19872213    Free PMC article.
Highly Cited.
Targeting Treg cells in cancer immunotherapy.
Atsushi Tanaka, Shimon Sakaguchi.
Eur J Immunol, 2019 Jul 02; 49(8). PMID: 31257581
Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression.
Chih-Hao Chang, Jing Qiu, +11 authors, Erika L Pearce.
Cell, 2015 Sep 01; 162(6). PMID: 26321679    Free PMC article.
Highly Cited.
The cancer metabolic reprogramming and immune response.
Longzheng Xia, Linda Oyang, +16 authors, Qianjin Liao.
Mol Cancer, 2021 Feb 07; 20(1). PMID: 33546704    Free PMC article.
Determinants of Resistance to Checkpoint Inhibitors.
Linda Tran, Dan Theodorescu.
Int J Mol Sci, 2020 Mar 01; 21(5). PMID: 32111080    Free PMC article.
Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection.
Jacob V Gorman, Gabriel Starbeck-Miller, +4 authors, John D Colgan.
J Immunol, 2014 Feb 26; 192(7). PMID: 24567532    Free PMC article.
Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial.
Scott J Antonia, José A López-Martin, +21 authors, Emiliano Calvo.
Lancet Oncol, 2016 Jun 09; 17(7). PMID: 27269741
Highly Cited.
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck.
Robert L Ferris, George Blumenschein, +20 authors, Maura L Gillison.
N Engl J Med, 2016 Oct 11; 375(19). PMID: 27718784    Free PMC article.
Highly Cited.
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.
Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.
Scott J Antonia, Augusto Villegas, +28 authors, PACIFIC Investigators.
N Engl J Med, 2017 Sep 09; 377(20). PMID: 28885881
Highly Cited.
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.
Shawn D Blackburn, Haina Shin, +7 authors, E John Wherry.
Nat Immunol, 2008 Dec 02; 10(1). PMID: 19043418    Free PMC article.
Highly Cited.
Induction of tolerogenic dendritic cells by IL-6-secreting CT26 colon carcinoma.
Aws Alshamsan.
Immunopharmacol Immunotoxicol, 2011 Oct 18; 34(3). PMID: 21999714
Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer.
Peter Schmid, Sylvia Adams, +16 authors, IMpassion130 Trial Investigators.
N Engl J Med, 2018 Oct 23; 379(22). PMID: 30345906
Highly Cited.
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer.
Scott Gettinger, Jungmin Choi, +23 authors, Katerina Politi.
Cancer Discov, 2017 Oct 14; 7(12). PMID: 29025772    Free PMC article.
Highly Cited.
A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma.
Andrea Wang-Gillam, Stacey Plambeck-Suess, +9 authors, Williams G Hawkins.
Invest New Drugs, 2012 Aug 07; 31(3). PMID: 22864469    Free PMC article.
Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy.
Suzanne L Topalian, Janis M Taube, Robert A Anders, Drew M Pardoll.
Nat Rev Cancer, 2016 Apr 16; 16(5). PMID: 27079802    Free PMC article.
Highly Cited. Review.
An acidic microenvironment impairs the generation of non-major histocompatibility complex-restricted killer cells.
B Müller, B Fischer, W Kreutz.
Immunology, 2000 Mar 11; 99(3). PMID: 10712667    Free PMC article.
Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer.
Naiyer A Rizvi, Matthew D Hellmann, +21 authors, Timothy A Chan.
Science, 2015 Mar 15; 348(6230). PMID: 25765070    Free PMC article.
Highly Cited.
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.
A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection.
P Som, H L Atkins, +10 authors, S V Zabinski.
J Nucl Med, 1980 Jul 01; 21(7). PMID: 7391842
Highly Cited.
Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.
Jonathan E Rosenberg, Jean Hoffman-Censits, +28 authors, Robert Dreicer.
Lancet, 2016 Mar 10; 387(10031). PMID: 26952546    Free PMC article.
Highly Cited.
Resistance to checkpoint blockade therapy through inactivation of antigen presentation.
Moshe Sade-Feldman, Yunxin J Jiao, +28 authors, Nir Hacohen.
Nat Commun, 2017 Oct 27; 8(1). PMID: 29070816    Free PMC article.
Highly Cited.
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial.
Roy S Herbst, Paul Baas, +16 authors, Edward B Garon.
Lancet, 2015 Dec 30; 387(10027). PMID: 26712084
Highly Cited.
Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial.
Anthony B El-Khoueiry, Bruno Sangro, +18 authors, Ignacio Melero.
Lancet, 2017 Apr 25; 389(10088). PMID: 28434648    Free PMC article.
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.
Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial.
Andrew X Zhu, Richard S Finn, +19 authors, KEYNOTE-224 investigators.
Lancet Oncol, 2018 Jun 08; 19(7). PMID: 29875066
Highly Cited.
Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial.
Jeffrey S Weber, Sandra P D'Angelo, +25 authors, James Larkin.
Lancet Oncol, 2015 Mar 22; 16(4). PMID: 25795410
Highly Cited.
Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial.
Padmanee Sharma, Margitta Retz, +16 authors, Matthew D Galsky.
Lancet Oncol, 2017 Jan 31; 18(3). PMID: 28131785
Highly Cited.
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.
Malignant gliomas display altered pH regulation by NHE1 compared with nontransformed astrocytes.
L A McLean, J Roscoe, +2 authors, P M Cala.
Am J Physiol Cell Physiol, 2001 Feb 07; 278(4). PMID: 10751317
Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.
Paul Nghiem, Shailender Bhatia, +28 authors, Suzanne L Topalian.
J Clin Oncol, 2019 Feb 07; 37(9). PMID: 30726175    Free PMC article.
Highly Cited.
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.
Dung T Le, Jennifer N Uram, +32 authors, Luis A Diaz.
N Engl J Med, 2015 Jun 02; 372(26). PMID: 26028255    Free PMC article.
Highly Cited.
An immunogenic personal neoantigen vaccine for patients with melanoma.
Patrick A Ott, Zhuting Hu, +37 authors, Catherine J Wu.
Nature, 2017 Jul 06; 547(7662). PMID: 28678778    Free PMC article.
Highly Cited.
Demethylation of the PD-1 Promoter Is Imprinted during the Effector Phase of CD8 T Cell Exhaustion.
Eunseon Ahn, Ben Youngblood, +3 authors, Rafi Ahmed.
J Virol, 2016 Jul 29; 90(19). PMID: 27466420    Free PMC article.
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.
Mechanisms of Resistance to Immune Checkpoint Blockade.
David Liu, Russell W Jenkins, Ryan J Sullivan.
Am J Clin Dermatol, 2018 Sep 28; 20(1). PMID: 30259383    Free PMC article.
CD28 and CTLA-4 coreceptor expression and signal transduction.
Christopher E Rudd, Alison Taylor, Helga Schneider.
Immunol Rev, 2009 May 12; 229(1). PMID: 19426212    Free PMC article.
Highly Cited. Review.
Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired.
Mojgan Ahmadzadeh, Laura A Johnson, +4 authors, Steven A Rosenberg.
Blood, 2009 May 09; 114(8). PMID: 19423728    Free PMC article.
Highly Cited.
B70 antigen is a second ligand for CTLA-4 and CD28.
M Azuma, D Ito, +4 authors, C Somoza.
Nature, 1993 Nov 04; 366(6450). PMID: 7694153
Highly Cited.
Molecular and genetic properties of tumors associated with local immune cytolytic activity.
Michael S Rooney, Sachet A Shukla, +2 authors, Nir Hacohen.
Cell, 2015 Jan 17; 160(1-2). PMID: 25594174    Free PMC article.
Highly Cited.
Emerging Opportunities and Challenges in Cancer Immunotherapy.
Theresa L Whiteside, Sandra Demaria, +2 authors, Ignacio Melero.
Clin Cancer Res, 2016 Apr 17; 22(8). PMID: 27084738    Free PMC article.
Highly Cited. Review.
Tumor Mutational Load and Immune Parameters across Metastatic Renal Cell Carcinoma Risk Groups.
Guillermo de Velasco, Diana Miao, +8 authors, Toni K Choueiri.
Cancer Immunol Res, 2016 Aug 20; 4(10). PMID: 27538576    Free PMC article.
The Warburg Effect: How Does it Benefit Cancer Cells?
Maria V Liberti, Jason W Locasale.
Trends Biochem Sci, 2016 Jan 19; 41(3). PMID: 26778478    Free PMC article.
Highly Cited. Review.
Acquired Resistance to Immune Checkpoint Inhibitors.
Adam J Schoenfeld, Matthew D Hellmann.
Cancer Cell, 2020 Apr 15; 37(4). PMID: 32289269    Free PMC article.
Immune checkpoint blockade immunotherapy to activate anti-tumour T-cell immunity.
Alan G Ramsay.
Br J Haematol, 2013 May 23; 162(3). PMID: 23691926
Signaling pathway and dysregulation of PD1 and its ligands in lymphoid malignancies.
Yi Xia, L Jeffrey Medeiros, Ken H Young.
Biochim Biophys Acta, 2015 Oct 04; 1865(1). PMID: 26432723    Free PMC article.
Viral immune evasion due to persistence of activated T cells without effector function.
A J Zajac, J N Blattman, +4 authors, R Ahmed.
J Exp Med, 1998 Dec 22; 188(12). PMID: 9858507    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.
Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
G J Freeman, A J Long, +16 authors, T Honjo.
J Exp Med, 2000 Oct 04; 192(7). PMID: 11015443    Free PMC article.
Highly Cited.
De-novo and acquired resistance to immune checkpoint targeting.
Nicholas L Syn, Michele W L Teng, Tony S K Mok, Ross A Soo.
Lancet Oncol, 2017 Dec 07; 18(12). PMID: 29208439
Highly Cited. Review.
VSIG-3 as a ligand of VISTA inhibits human T-cell function.
Jinghua Wang, Guoping Wu, +17 authors, Vassilios Kalabokis.
Immunology, 2018 Sep 17; 156(1). PMID: 30220083    Free PMC article.
Highly Cited.
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.
Blockade of Na/H exchanger stimulates glioma tumor immunogenicity and enhances combinatorial TMZ and anti-PD-1 therapy.
Xiudong Guan, Md Nabiul Hasan, +7 authors, Dandan Sun.
Cell Death Dis, 2018 Sep 29; 9(10). PMID: 30262908    Free PMC article.
Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.
Brian I Rini, Elizabeth R Plimack, +25 authors, KEYNOTE-426 Investigators.
N Engl J Med, 2019 Feb 20; 380(12). PMID: 30779529
Highly Cited.
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.
Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor.
H Nishimura, M Nose, +2 authors, T Honjo.
Immunity, 1999 Sep 15; 11(2). PMID: 10485649
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.
CTLA-4 trafficking and surface expression.
Elke Valk, Christopher E Rudd, Helga Schneider.
Trends Immunol, 2008 May 13; 29(6). PMID: 18468488    Free PMC article.
Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial.
Howard L Kaufman, Jeffery Russell, +15 authors, Paul Nghiem.
Lancet Oncol, 2016 Sep 07; 17(10). PMID: 27592805    Free PMC article.
Highly Cited.
Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response.
Peng Jiang, Shengqing Gu, +12 authors, X Shirley Liu.
Nat Med, 2018 Aug 22; 24(10). PMID: 30127393    Free PMC article.
Highly Cited.
Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Metastatic Melanoma.
Tuba N Gide, James S Wilmott, Richard A Scolyer, Georgina V Long.
Clin Cancer Res, 2017 Nov 12; 24(6). PMID: 29127120
First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study.
Arjun V Balar, Daniel Castellano, +12 authors, Joaquim Bellmunt.
Lancet Oncol, 2017 Oct 03; 18(11). PMID: 28967485
Highly Cited.
Identification and validation of a tumor-infiltrating Treg transcriptional signature conserved across species and tumor types.
Angela M Magnuson, Evgeny Kiner, +8 authors, Christophe Benoist.
Proc Natl Acad Sci U S A, 2018 Oct 24; 115(45). PMID: 30348759    Free PMC article.
TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM.
Alice L Hung, Russell Maxwell, +20 authors, Michael Lim.
Oncoimmunology, 2018 Sep 18; 7(8). PMID: 30221069    Free PMC article.
Highly Cited.
PD-1 blockade induces responses by inhibiting adaptive immune resistance.
Paul C Tumeh, Christina L Harview, +23 authors, Antoni Ribas.
Nature, 2014 Nov 28; 515(7528). PMID: 25428505    Free PMC article.
Highly Cited.
T Cell Dysfunction in Cancer Immunity and Immunotherapy.
Anliang Xia, Yan Zhang, +2 authors, Xiao-Jie Lu.
Front Immunol, 2019 Aug 06; 10. PMID: 31379886    Free PMC article.
Highly Cited. Review.
Glycogen synthase kinase 3: an emerging therapeutic target.
Hagit Eldar-Finkelman.
Trends Mol Med, 2002 Mar 07; 8(3). PMID: 11879773
Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD-1 therapy in metastatic melanoma patients.
Hojabr Kakavand, Louise A Jackett, +7 authors, Richard A Scolyer.
Mod Pathol, 2017 Aug 05; 30(12). PMID: 28776578
LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model.
Ruea-Yea Huang, Cheryl Eppolito, +3 authors, Kunle Odunsi.
Oncotarget, 2015 Sep 01; 6(29). PMID: 26318293    Free PMC article.
Highly Cited.
Combinations of Bevacizumab With Cancer Immunotherapy.
Daniel S Chen, Herbert Hurwitz.
Cancer J, 2018 Aug 18; 24(4). PMID: 30119083
Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine.
Ji Zhang, Natalya N Pavlova, Craig B Thompson.
EMBO J, 2017 Apr 20; 36(10). PMID: 28420743    Free PMC article.
Highly Cited. Review.
Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma.
Robert J Motzer, Nizar M Tannir, +30 authors, CheckMate 214 Investigators.
N Engl J Med, 2018 Mar 22; 378(14). PMID: 29562145    Free PMC article.
Highly Cited.
Oncolytic Immunotherapy: Dying the Right Way is a Key to Eliciting Potent Antitumor Immunity.
Zong Sheng Guo, Zuqiang Liu, David L Bartlett.
Front Oncol, 2014 May 02; 4. PMID: 24782985    Free PMC article.
Highly Cited. Review.
Dendritic cells in the cancer microenvironment.
Yang Ma, Galina V Shurin, Zhu Peiyuan, Michael R Shurin.
J Cancer, 2013 Feb 07; 4(1). PMID: 23386903    Free PMC article.
Highly Cited.
B7-H3, a checkpoint molecule, as a target for cancer immunotherapy.
Shuo Yang, Wei Wei, Qi Zhao.
Int J Biol Sci, 2020 May 14; 16(11). PMID: 32398947    Free PMC article.
Pembrolizumab for the treatment of non-small-cell lung cancer.
Edward B Garon, Naiyer A Rizvi, +25 authors, KEYNOTE-001 Investigators.
N Engl J Med, 2015 Apr 22; 372(21). PMID: 25891174
Highly Cited.
Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy.
Alexander M M Eggermont, Vanna Chiarion-Sileni, +24 authors, Alessandro Testori.
N Engl J Med, 2016 Oct 09; 375(19). PMID: 27717298    Free PMC article.
Highly Cited.
Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications.
Aitziber Buqué, Norma Bloy, +12 authors, Lorenzo Galluzzi.
Oncoimmunology, 2015 Jul 03; 4(4). PMID: 26137403    Free PMC article.
The expression of the immune checkpoint regulator VISTA correlates with improved overall survival in pT1/2 tumor stages in esophageal adenocarcinoma.
Heike Loeser, Max Kraemer, +9 authors, Alexander Quaas.
Oncoimmunology, 2019 May 10; 8(5). PMID: 31069143    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.
Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.
Hossein Borghaei, Luis Paz-Ares, +25 authors, Julie R Brahmer.
N Engl J Med, 2015 Sep 29; 373(17). PMID: 26412456    Free PMC article.
Highly Cited.
Polarization of macrophages towards M1 phenotype by a combination of 2-deoxy-d-glucose and radiation: Implications for tumor therapy.
Abdullah Farooque, Farhat Afrin, Jawahar Singh Adhikari, Bilikere Srinivasa Rao Dwarakanath.
Immunobiology, 2015 Nov 26; 221(2). PMID: 26597503
Evolution of Neoantigen Landscape during Immune Checkpoint Blockade in Non-Small Cell Lung Cancer.
Valsamo Anagnostou, Kellie N Smith, +26 authors, Victor E Velculescu.
Cancer Discov, 2016 Dec 30; 7(3). PMID: 28031159    Free PMC article.
Highly Cited.
New monoclonal antibodies against B-cell antigens: possible new strategies for diagnosis of primary cutaneous B-cell lymphomas.
D Fanoni, S Tavecchio, +5 authors, E Berti.
Immunol Lett, 2010 Oct 19; 134(2). PMID: 20951741
Current Challenges in Cancer Immunotherapy: Multimodal Approaches to Improve Efficacy and Patient Response Rates.
Manpreet Sambi, Leila Bagheri, Myron R Szewczuk.
J Oncol, 2019 Apr 04; 2019. PMID: 30941175    Free PMC article.
Highly Cited. Review.
Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy.
Vivek Kumar, Neha Chaudhary, +3 authors, Abhinav B Chandra.
Front Pharmacol, 2017 Feb 24; 8. PMID: 28228726    Free PMC article.
Highly Cited. Review.
The reverse Warburg effect: glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts.
Gloria Bonuccelli, Diana Whitaker-Menezes, +13 authors, Michael P Lisanti.
Cell Cycle, 2010 May 25; 9(10). PMID: 20495363
Highly Cited.
A Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non-Small Cell Lung Cancer.
David L Rimm, Gang Han, +17 authors, Ignacio I Wistuba.
JAMA Oncol, 2017 Mar 10; 3(8). PMID: 28278348    Free PMC article.
Highly Cited.
The MHC I loading complex: a multitasking machinery in adaptive immunity.
Sabine Hulpke, Robert Tampé.
Trends Biochem Sci, 2013 Jul 16; 38(8). PMID: 23849087
Mechanisms of resistance to immune checkpoint inhibitors.
Russell W Jenkins, David A Barbie, Keith T Flaherty.
Br J Cancer, 2018 Jan 11; 118(1). PMID: 29319049    Free PMC article.
Highly Cited. Review.
Nutrient Competition: A New Axis of Tumor Immunosuppression.
Madhusudhanan Sukumar, Rahul Roychoudhuri, Nicholas P Restifo.
Cell, 2015 Sep 12; 162(6). PMID: 26359979    Free PMC article.
The Cancer Epigenome: Exploiting Its Vulnerabilities for Immunotherapy.
Helen Loo Yau, Ilias Ettayebi, Daniel D De Carvalho.
Trends Cell Biol, 2018 Aug 30; 29(1). PMID: 30153961
Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma.
Robert Chen, Pier Luigi Zinzani, +15 authors, KEYNOTE-087.
J Clin Oncol, 2017 Apr 26; 35(19). PMID: 28441111    Free PMC article.
Highly Cited.
Immunotherapy in Non-Small Cell Lung Cancer: Facts and Hopes.
Deborah B Doroshow, Miguel F Sanmamed, +6 authors, Roy S Herbst.
Clin Cancer Res, 2019 Mar 03; 25(15). PMID: 30824587    Free PMC article.
Highly Cited. Review.
The Immune Revolution: A Case for Priming, Not Checkpoint.
Robert H Vonderheide.
Cancer Cell, 2018 Apr 11; 33(4). PMID: 29634944    Free PMC article.
Highly Cited. Review.
The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived suppressor cells.
Chunwan Lu, Priscilla S Redd, +2 authors, Kebin Liu.
Oncoimmunology, 2017 Jan 27; 5(12). PMID: 28123883    Free PMC article.
Highly Cited.
Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment.
E John Wherry, Joseph N Blattman, +2 authors, Rafi Ahmed.
J Virol, 2003 Mar 29; 77(8). PMID: 12663797    Free PMC article.
Highly Cited.
Next generation of immune checkpoint inhibitors and beyond.
Julian A Marin-Acevedo, ErinMarie O Kimbrough, Yanyan Lou.
J Hematol Oncol, 2021 Mar 21; 14(1). PMID: 33741032    Free PMC article.
Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study.
Stephen M Ansell, Monique C Minnema, +15 authors, Andrew Grigg.
J Clin Oncol, 2019 Jan 09; 37(6). PMID: 30620669    Free PMC article.
Highly Cited.
The CD28 signaling pathway regulates glucose metabolism.
Kenneth A Frauwirth, James L Riley, +6 authors, Craig B Thompson.
Immunity, 2002 Jul 18; 16(6). PMID: 12121659
Highly Cited.
Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade.
Joseph L Benci, Bihui Xu, +16 authors, Andy J Minn.
Cell, 2016 Dec 03; 167(6). PMID: 27912061    Free PMC article.
Highly Cited.
Treg-mediated acquired resistance to immune checkpoint inhibitors.
Reem Saleh, Eyad Elkord.
Cancer Lett, 2019 May 13; 457. PMID: 31078738
Myeloid-Derived Suppressor Cells Hinder the Anti-Cancer Activity of Immune Checkpoint Inhibitors.
Rebekka Weber, Viktor Fleming, +5 authors, Viktor Umansky.
Front Immunol, 2018 Jun 27; 9. PMID: 29942309    Free PMC article.
Highly Cited. Review.
Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes.
Arianna Calcinotto, Paola Filipazzi, +15 authors, Licia Rivoltini.
Cancer Res, 2012 May 18; 72(11). PMID: 22593198
Highly Cited.
B7-1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in the absence of CD28.
F Fallarino, P E Fields, T F Gajewski.
J Exp Med, 1998 Jul 07; 188(1). PMID: 9653097    Free PMC article.
Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study.
Hyun Cheol Chung, Willeke Ros, +9 authors, Alexandra Leary.
J Clin Oncol, 2019 Apr 04; 37(17). PMID: 30943124
Highly Cited.
Tumor Mutational Burden and Response Rate to PD-1 Inhibition.
Mark Yarchoan, Alexander Hopkins, Elizabeth M Jaffee.
N Engl J Med, 2017 Dec 21; 377(25). PMID: 29262275    Free PMC article.
Highly Cited.
Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma.
Nienke van Rooij, Marit M van Buuren, +14 authors, Ton N Schumacher.
J Clin Oncol, 2013 Sep 18; 31(32). PMID: 24043743    Free PMC article.
Highly Cited.
Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy.
Christian Blank, Thomas F Gajewski, Andreas Mackensen.
Cancer Immunol Immunother, 2004 Dec 16; 54(4). PMID: 15599732
Highly Cited. Review.
The B7 family of immune-regulatory ligands.
Mary Collins, Vincent Ling, Beatriz M Carreno.
Genome Biol, 2005 Jun 18; 6(6). PMID: 15960813    Free PMC article.
Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial.
Louis Fehrenbacher, Alexander Spira, +16 authors, POPLAR Study Group.
Lancet, 2016 Mar 14; 387(10030). PMID: 26970723
Highly Cited.
Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.
Robert J Motzer, Konstantin Penkov, +25 authors, Toni K Choueiri.
N Engl J Med, 2019 Feb 20; 380(12). PMID: 30779531    Free PMC article.
Highly Cited.
Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.
Ryan D Michalek, Valerie A Gerriets, +6 authors, Jeffrey C Rathmell.
J Immunol, 2011 Feb 15; 186(6). PMID: 21317389    Free PMC article.
Highly Cited.
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.
A guide to immunometabolism for immunologists.
Luke A J O'Neill, Rigel J Kishton, Jeff Rathmell.
Nat Rev Immunol, 2016 Jul 12; 16(9). PMID: 27396447    Free PMC article.
Highly Cited. Review.
Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.
I Puzanov, A Diab, +19 authors, Society for Immunotherapy of Cancer Toxicity Management Working Group.
J Immunother Cancer, 2017 Nov 23; 5(1). PMID: 29162153    Free PMC article.
Highly Cited.
Structural basis for cancer immunotherapy by the first-in-class checkpoint inhibitor ipilimumab.
Udupi A Ramagopal, Weifeng Liu, +10 authors, Steven C Almo.
Proc Natl Acad Sci U S A, 2017 May 10; 114(21). PMID: 28484017    Free PMC article.
Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression.
Christopher Groth, Xiaoying Hu, +4 authors, Viktor Umansky.
Br J Cancer, 2018 Nov 11; 120(1). PMID: 30413826    Free PMC article.
Highly Cited. Review.
T-cell tolerance or function is determined by combinatorial costimulatory signals.
Roza Nurieva, Sunil Thomas, +5 authors, Chen Dong.
EMBO J, 2006 May 26; 25(11). PMID: 16724117    Free PMC article.
FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors.
Leigh Marcus, Steven J Lemery, Patricia Keegan, Richard Pazdur.
Clin Cancer Res, 2019 Feb 23; 25(13). PMID: 30787022
Highly Cited.
The novel negative checkpoint regulator VISTA is expressed in gastric carcinoma and associated with PD-L1/PD-1: A future perspective for a combined gastric cancer therapy?
Christine Böger, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken.
Oncoimmunology, 2017 May 17; 6(4). PMID: 28507801    Free PMC article.
Harnessing tumor-associated macrophages as aids for cancer immunotherapy.
Xiaolei Li, Rui Liu, +4 authors, Yufang Shi.
Mol Cancer, 2019 Dec 07; 18(1). PMID: 31805946    Free PMC article.
Genetic evolution of T-cell resistance in the course of melanoma progression.
Antje Sucker, Fang Zhao, +16 authors, Annette Paschen.
Clin Cancer Res, 2014 Oct 09; 20(24). PMID: 25294904    Free PMC article.
Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial.
Vicky Makker, Drew Rasco, +13 authors, Matthew Taylor.
Lancet Oncol, 2019 Mar 30; 20(5). PMID: 30922731
Highly Cited.
Molecular and cellular insights into T cell exhaustion.
E John Wherry, Makoto Kurachi.
Nat Rev Immunol, 2015 Jul 25; 15(8). PMID: 26205583    Free PMC article.
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.
Dendritic Cells and Cancer: From Biology to Therapeutic Intervention.
Ben Wylie, Christophe Macri, Justine D Mintern, Jason Waithman.
Cancers (Basel), 2019 Apr 14; 11(4). PMID: 30979057    Free PMC article.
Molecular Pathways: Targeting B7-H3 (CD276) for Human Cancer Immunotherapy.
Elodie Picarda, Kim C Ohaegbulam, Xingxing Zang.
Clin Cancer Res, 2016 May 22; 22(14). PMID: 27208063    Free PMC article.
Highly Cited.
Neoantigens in cancer immunotherapy.
Ton N Schumacher, Robert D Schreiber.
Science, 2015 Apr 04; 348(6230). PMID: 25838375
Highly Cited. Review.
Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation.
Ana C Anderson, Nicole Joller, Vijay K Kuchroo.
Immunity, 2016 May 19; 44(5). PMID: 27192565    Free PMC article.
Highly Cited. Review.
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.
TIM-3, a promising target for cancer immunotherapy.
Yayi He, Jie Cao, +3 authors, Fred R Hirsch.
Onco Targets Ther, 2018 Nov 10; 11. PMID: 30410357    Free PMC article.
Highly Cited. Review.
Identification and characterization of galectin-9, a novel beta-galactoside-binding mammalian lectin.
J Wada, Y S Kanwar.
J Biol Chem, 1997 Feb 28; 272(9). PMID: 9038233
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.
Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota.
Marie Vétizou, Jonathan M Pitt, +35 authors, Laurence Zitvogel.
Science, 2015 Nov 07; 350(6264). PMID: 26541610    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.
Dichloroacetate should be considered with platinum-based chemotherapy in hypoxic tumors rather than as a single agent in advanced non-small cell lung cancer.
Edward B Garon, Heather R Christofk, +13 authors, Dennis J Slamon.
J Cancer Res Clin Oncol, 2014 Jan 21; 140(3). PMID: 24442098    Free PMC article.
Mechanisms of Resistance to Immune Checkpoint Blockade: Why Does Checkpoint Inhibitor Immunotherapy Not Work for All Patients?
Charlene M Fares, Eliezer M Van Allen, +2 authors, Siwen Hu-Lieskovan.
Am Soc Clin Oncol Educ Book, 2019 May 18; 39. PMID: 31099674
Highly Cited. Review.
Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study.
Thomas Powles, Peter H O'Donnell, +16 authors, Noah M Hahn.
JAMA Oncol, 2017 Aug 18; 3(9). PMID: 28817753    Free PMC article.
Highly Cited.
Recognition of nectin-2 by the natural killer cell receptor T cell immunoglobulin and ITIM domain (TIGIT).
Felix A Deuss, Benjamin S Gully, Jamie Rossjohn, Richard Berry.
J Biol Chem, 2017 May 19; 292(27). PMID: 28515320    Free PMC article.
VISTA: an immune regulatory protein checking tumor and immune cells in cancer immunotherapy.
Xing Huang, Xiaozhen Zhang, +5 authors, Tingbo Liang.
J Hematol Oncol, 2020 Jul 01; 13(1). PMID: 32600443    Free PMC article.
Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study.
Michael J Overman, Ray McDermott, +13 authors, Thierry André.
Lancet Oncol, 2017 Jul 25; 18(9). PMID: 28734759    Free PMC article.
Highly Cited.
Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors.
Kristian M Hargadon, Coleman E Johnson, Corey J Williams.
Int Immunopharmacol, 2018 Jul 11; 62. PMID: 29990692
Highly Cited. Review.
Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth.
Ilenia Pacella, Claudio Procaccini, +17 authors, Silvia Piconese.
Proc Natl Acad Sci U S A, 2018 Jun 27; 115(28). PMID: 29941600    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.
Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression.
Angel Garcia-Diaz, Daniel Sanghoon Shin, +16 authors, Antoni Ribas.
Cell Rep, 2017 May 13; 19(6). PMID: 28494868    Free PMC article.
Highly Cited.
First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer.
Leora Horn, Aaron S Mansfield, +19 authors, IMpower133 Study Group.
N Engl J Med, 2018 Oct 04; 379(23). PMID: 30280641
Highly Cited.
Not all immune-checkpoint inhibitors are created equal: Meta-analysis and systematic review of immune-related adverse events in cancer trials.
B El Osta, F Hu, +2 authors, S-C Tang.
Crit Rev Oncol Hematol, 2017 Oct 27; 119. PMID: 29065979
Systematic Review.
Fuel feeds function: energy metabolism and the T-cell response.
Casey J Fox, Peter S Hammerman, Craig B Thompson.
Nat Rev Immunol, 2005 Oct 22; 5(11). PMID: 16239903
Highly Cited. Review.
Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies.
Karl S Peggs, Sergio A Quezada, +2 authors, James P Allison.
J Exp Med, 2009 Jul 08; 206(8). PMID: 19581407    Free PMC article.
Highly Cited.
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer.
Julie Brahmer, Karen L Reckamp, +22 authors, David R Spigel.
N Engl J Med, 2015 Jun 02; 373(2). PMID: 26028407    Free PMC article.
Highly Cited.
Polarization of tumor-associated macrophages: a novel strategy for vascular normalization and antitumor immunity.
Yuhui Huang, Matija Snuderl, Rakesh K Jain.
Cancer Cell, 2011 Jan 22; 19(1). PMID: 21251607    Free PMC article.
Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study.
Hans J Hammers, Elizabeth R Plimack, +12 authors, Asim Amin.
J Clin Oncol, 2017 Jul 06; 35(34). PMID: 28678668    Free PMC article.
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.
Cancer cell metabolic reprogramming: a keystone for the response to immunotherapy.
Michaël Cerezo, Stéphane Rocchi.
Cell Death Dis, 2020 Nov 13; 11(11). PMID: 33177494    Free PMC article.
Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity.
Fumiya Hirano, Katsumi Kaneko, +9 authors, Lieping Chen.
Cancer Res, 2005 Feb 12; 65(3). PMID: 15705911
Highly Cited.
New Insights Into the Cancer-Microbiome-Immune Axis: Decrypting a Decade of Discoveries.
Tejeshwar Jain, Prateek Sharma, +2 authors, Vikas Dudeja.
Front Immunol, 2021 Mar 13; 12. PMID: 33708214    Free PMC article.
TIGIT Enhances Antigen-Specific Th2 Recall Responses and Allergic Disease.
Evangelia Kourepini, Nikolaos Paschalidis, +3 authors, Vily Panoutsakopoulou.
J Immunol, 2016 Mar 27; 196(9). PMID: 27016609
Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study.
Andrea B Apolo, Jeffrey R Infante, +14 authors, James L Gulley.
J Clin Oncol, 2017 Apr 05; 35(19). PMID: 28375787    Free PMC article.
Highly Cited.
Cervical cancer cell-derived interleukin-6 impairs CCR7-dependent migration of MMP-9-expressing dendritic cells.
Jennifer Pahne-Zeppenfeld, Nadine Schröer, +4 authors, Sigrun Smola.
Int J Cancer, 2013 Oct 19; 134(9). PMID: 24136650
Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma.
Evan J Lipson, Charles G Drake.
Clin Cancer Res, 2011 Sep 09; 17(22). PMID: 21900389    Free PMC article.
Highly Cited. Review.
TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action.
Wenwen Du, Min Yang, +5 authors, Binfeng Lu.
Int J Mol Sci, 2017 Mar 17; 18(3). PMID: 28300768    Free PMC article.
Biased activation of human T lymphocytes due to low extracellular pH is antagonized by B7/CD28 costimulation.
M Bosticardo, S Ariotti, +3 authors, F Novelli.
Eur J Immunol, 2001 Sep 06; 31(9). PMID: 11536182
CD25+ CD4+ regulatory T-cells in cancer.
David C Linehan, Peter S Goedegebuure.
Immunol Res, 2005 Aug 18; 32(1-3). PMID: 16106066
Immune checkpoint inhibitors in cancer therapy.
Eika S Webb, Peng Liu, +3 authors, Yao-He Wang.
J Biomed Res, 2017 Sep 04; 32(5). PMID: 28866656    Free PMC article.
Glutamine uptake and metabolism are coordinately regulated by ERK/MAPK during T lymphocyte activation.
Erikka L Carr, Alina Kelman, +5 authors, Kenneth A Frauwirth.
J Immunol, 2010 Jun 18; 185(2). PMID: 20554958    Free PMC article.
Highly Cited.
PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma.
Michael R Migden, Danny Rischin, +34 authors, Matthew G Fury.
N Engl J Med, 2018 Jun 05; 379(4). PMID: 29863979
Highly Cited.
Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial.
Charles S Fuchs, Toshihiko Doi, +26 authors, Harry H Yoon.
JAMA Oncol, 2018 Mar 16; 4(5). PMID: 29543932    Free PMC article.
Highly Cited.
Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade.
Kristen E Pauken, Morgan A Sammons, +16 authors, E John Wherry.
Science, 2016 Oct 30; 354(6316). PMID: 27789795    Free PMC article.
Highly Cited.
Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells.
Candace M Cham, Gregory Driessens, James P O'Keefe, Thomas F Gajewski.
Eur J Immunol, 2008 Sep 16; 38(9). PMID: 18792400    Free PMC article.
Highly Cited.
mTOR Regulation of Glycolytic Metabolism in T Cells.
Robert J Salmond.
Front Cell Dev Biol, 2018 Oct 16; 6. PMID: 30320109    Free PMC article.
Dendritic Cells and CD8 T Cell Immunity in Tumor Microenvironment.
Chunmei Fu, Aimin Jiang.
Front Immunol, 2019 Jan 09; 9. PMID: 30619378    Free PMC article.
Highly Cited. Review.
Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab.
Christiane Meyer, Laurène Cagnon, +6 authors, Daniel E Speiser.
Cancer Immunol Immunother, 2013 Dec 21; 63(3). PMID: 24357148
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.
Neoantigen vaccine: an emerging tumor immunotherapy.
Miao Peng, Yongzhen Mo, +10 authors, Zhaoyang Zeng.
Mol Cancer, 2019 Aug 25; 18(1). PMID: 31443694    Free PMC article.
Highly Cited. Review.
Depletion of CD4+CD25+ regulatory T cells promotes a tumor-specific immune response in pancreas cancer-bearing mice.
Carsten T Viehl, Todd T Moore, +5 authors, David C Linehan.
Ann Surg Oncol, 2006 Sep 05; 13(9). PMID: 16952047
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.
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.
Dung T Le, Jennifer N Durham, +43 authors, Luis A Diaz.
Science, 2017 Jun 10; 357(6349). PMID: 28596308    Free PMC article.
Highly Cited.
A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma.
Omid Hamid, Henrik Schmidt, +9 authors, David Berman.
J Transl Med, 2011 Nov 30; 9. PMID: 22123319    Free PMC article.
Highly Cited.
PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
Stephen M Ansell, Alexander M Lesokhin, +16 authors, Philippe Armand.
N Engl J Med, 2014 Dec 09; 372(4). PMID: 25482239    Free PMC article.
Highly Cited.
Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial.
R Wendel Naumann, Antoine Hollebecque, +16 authors, Kathleen N Moore.
J Clin Oncol, 2019 Sep 06; 37(31). PMID: 31487218    Free PMC article.
Murine B7-H3 is a negative regulator of T cells.
Durbaka V R Prasad, Thang Nguyen, +4 authors, Chen Dong.
J Immunol, 2004 Aug 06; 173(4). PMID: 15294965
Twelve unanswered questions in cancer inspired by the life and work of Leland Chung: "if this is true, what does it imply"?
Melvin Li, Anna Lk Gonye, +13 authors, Kenneth J Pienta.
Am J Clin Exp Urol, 2021 Sep 21; 9(4). PMID: 34541023    Free PMC article.
Tumor-Derived Extracellular Vesicles: A Means of Co-opting Macrophage Polarization in the Tumor Microenvironment.
Theodore Reed, Jeffrey Schorey, Crislyn D'Souza-Schorey.
Front Cell Dev Biol, 2021 Oct 26; 9. PMID: 34692700    Free PMC article.
Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment.
Alain E Andrea, Andrada Chiron, +3 authors, Salima Hacein-Bey-Abina.
Front Immunol, 2022 Feb 26; 13. PMID: 35211124    Free PMC article.
Impact of Diets on Response to Immune Checkpoint Inhibitors (ICIs) Therapy against Tumors.
Xin Zhang, Huiqin Li, +4 authors, Yonghan He.
Life (Basel), 2022 Mar 26; 12(3). PMID: 35330159    Free PMC article.
Predictive Markers for Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.
Ryota Ushio, Shuji Murakami, Haruhiro Saito.
J Clin Med, 2022 Apr 13; 11(7). PMID: 35407463    Free PMC article.