Review
. 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 
Affiliations
  • PMID: 34268109
  •     184 References
  •     5 citations

Abstract

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.

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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
Review.
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.
Review.
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.
Review.
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.
Review.
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.
Review.
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.
Review.
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.
Review.
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.
Review.
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
Review.
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.
Review.
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.
Review.
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.
Review.
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.
Review.