Review
. 2018 Aug; 13(5):383-395.
doi: 10.1007/s11899-018-0471-9.

Strategies for Predicting Response to Checkpoint Inhibitors

Roberta Zappasodi 1 Jedd D Wolchok 1 Taha Merghoub 2 
Affiliations
  • PMID: 30159703
  •     118 References
  •     17 citations

Abstract

Purpose Of Review: Despite the clinical successes of immune checkpoint blockade across multiple tumor types, many patients do not respond to these therapies or become resistant after an initial response. This underscores the need to improve our understanding of the molecular determinants of response to guide more personalized and rational utilization of these therapies. Here, we describe available biomarkers of checkpoint blockade activity by classifying them into four major categories: tumor-intrinsic, immune microenvironmental, host-related, and dynamic factors.

Recent Findings: The clinical experience accumulated thus far with checkpoint blockade now offers the opportunity to comprehensively study the molecular and immune features associated with response. This is yielding a growing set of biomarkers whose integration will be key to more accurately predict clinical outcome. We propose a model for systematic assessment of available baseline and dynamic biomarkers in relationship with patients' outcomes. This will improve our understanding of the tumor-immune interactions and dynamics that predict a clinical response and will provide key information to develop more personalized and effective treatment strategies.

Keywords: Gut microbiota; Immune checkpoint; Immunotherapy; Neoantigens; Response biomarkers; T cells.

Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.
Haidong Dong, Scott E Strome, +10 authors, Lieping Chen.
Nat Med, 2002 Jul 02; 8(8). PMID: 12091876
Highly Cited.
The three Es of cancer immunoediting.
Gavin P Dunn, Lloyd J Old, Robert D Schreiber.
Annu Rev Immunol, 2004 Mar 23; 22. PMID: 15032581
Highly Cited. Review.
IFN unresponsiveness in LNCaP cells due to the lack of JAK1 gene expression.
Gavin P Dunn, Kathleen C F Sheehan, Lloyd J Old, Robert D Schreiber.
Cancer Res, 2005 Apr 19; 65(8). PMID: 15833880
Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer.
Yuichiro Ohigashi, Masayuki Sho, +12 authors, Yoshiyuki Nakajima.
Clin Cancer Res, 2005 Apr 20; 11(8). PMID: 15837746
Highly Cited.
Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance.
Changping Wu, Yibei Zhu, +3 authors, Ning Xu.
Acta Histochem, 2006 Mar 15; 108(1). PMID: 16530813
Highly Cited.
Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up.
R Houston Thompson, Susan M Kuntz, +11 authors, Eugene D Kwon.
Cancer Res, 2006 Apr 06; 66(7). PMID: 16585157
Highly Cited.
Type, density, and location of immune cells within human colorectal tumors predict clinical outcome.
Jérôme Galon, Anne Costes, +13 authors, Franck Pagès.
Science, 2006 Sep 30; 313(5795). PMID: 17008531
Highly Cited.
Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma.
Andrew T Parsa, James S Waldron, +10 authors, Russell O Pieper.
Nat Med, 2006 Dec 13; 13(1). PMID: 17159987
Highly Cited.
Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer.
Junzo Hamanishi, Masaki Mandai, +9 authors, Shingo Fujii.
Proc Natl Acad Sci U S A, 2007 Mar 16; 104(9). PMID: 17360651    Free PMC article.
Highly Cited.
Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1).
Michal Marzec, Qian Zhang, +8 authors, Mariusz A Wasik.
Proc Natl Acad Sci U S A, 2008 Dec 18; 105(52). PMID: 19088198    Free PMC article.
Highly Cited.
The first 30 years of p53: growing ever more complex.
Arnold J Levine, Moshe Oren.
Nat Rev Cancer, 2009 Sep 25; 9(10). PMID: 19776744    Free PMC article.
Highly Cited. Review.
In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer.
Franck Pagès, Amos Kirilovsky, +12 authors, Jérôme Galon.
J Clin Oncol, 2009 Oct 28; 27(35). PMID: 19858404
Highly Cited.
Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival.
Geoffrey Y Ku, Jianda Yuan, +7 authors, Jedd D Wolchok.
Cancer, 2010 Feb 10; 116(7). PMID: 20143434    Free PMC article.
Highly Cited.
Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial.
Bradley C Carthon, Jedd D Wolchok, +8 authors, Padmanee Sharma.
Clin Cancer Res, 2010 May 13; 16(10). PMID: 20460488    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.
Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.
Michael R Green, Stefano Monti, +9 authors, Margaret A Shipp.
Blood, 2010 Jul 16; 116(17). PMID: 20628145    Free PMC article.
Highly Cited.
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
Caroline Robert, Luc Thomas, +21 authors, Jedd D Wolchok.
N Engl J Med, 2011 Jun 07; 364(26). PMID: 21639810
Highly Cited.
Unraveling the mechanism of BRCA2 in homologous recombination.
William K Holloman.
Nat Struct Mol Biol, 2011 Jul 07; 18(7). PMID: 21731065    Free PMC article.
Review.
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.
An immune-active tumor microenvironment favors clinical response to ipilimumab.
Rui-Ru Ji, Scott D Chasalow, +9 authors, Vafa Shahabi.
Cancer Immunol Immunother, 2011 Dec 08; 61(7). PMID: 22146893
Highly Cited.
The immune contexture in human tumours: impact on clinical outcome.
Wolf Herman Fridman, Franck Pagès, Catherine Sautès-Fridman, Jérôme Galon.
Nat Rev Cancer, 2012 Mar 16; 12(4). PMID: 22419253
Highly Cited. Review.
Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape.
Janis M Taube, Robert A Anders, +8 authors, Lieping Chen.
Sci Transl Med, 2012 Mar 31; 4(127). PMID: 22461641    Free PMC article.
Highly Cited.
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L Topalian, F Stephen Hodi, +27 authors, Mario Sznol.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658127    Free PMC article.
Highly Cited.
Biomarkers on melanoma patient T cells associated with ipilimumab treatment.
Wenshi Wang, Daohai Yu, +6 authors, Jeffrey S Weber.
J Transl Med, 2012 Jul 14; 10. PMID: 22788688    Free PMC article.
A critical review of the role of Fc gamma receptor polymorphisms in the response to monoclonal antibodies in cancer.
James D Mellor, Michael P Brown, +2 authors, Alexander Dobrovic.
J Hematol Oncol, 2013 Jan 05; 6. PMID: 23286345    Free PMC article.
Highly Cited. Review.
Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival.
J Delyon, C Mateus, +7 authors, C Robert.
Ann Oncol, 2013 Feb 27; 24(6). PMID: 23439861
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.
Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies.
Yannick Bulliard, Rose Jolicoeur, +6 authors, Jennifer L Brogdon.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897982    Free PMC article.
Highly Cited.
Signatures of mutational processes in human cancer.
Ludmil B Alexandrov, Serena Nik-Zainal, +72 authors, Michael R Stratton.
Nature, 2013 Aug 16; 500(7463). PMID: 23945592    Free PMC article.
Highly Cited.
Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.
Gabriela Bindea, Bernhard Mlecnik, +14 authors, Jérôme Galon.
Immunity, 2013 Oct 22; 39(4). PMID: 24138885
Highly Cited.
Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial.
Jason R Westin, Fuliang Chu, +19 authors, Sattva S Neelapu.
Lancet Oncol, 2013 Dec 18; 15(1). PMID: 24332512    Free PMC article.
Highly Cited.
Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab.
Ahmad A Tarhini, Howard Edington, +9 authors, John M Kirkwood.
PLoS One, 2014 Feb 06; 9(2). PMID: 24498358    Free PMC article.
Highly Cited.
CTLA4 blockade broadens the peripheral T-cell receptor repertoire.
Lidia Robert, Jennifer Tsoi, +11 authors, Antoni Ribas.
Clin Cancer Res, 2014 Mar 04; 20(9). PMID: 24583799    Free PMC article.
Highly Cited.
Increased frequency of ICOS+ CD4 T cells as a pharmacodynamic biomarker for anti-CTLA-4 therapy.
Derek Ng Tang, Yu Shen, +5 authors, Padmanee Sharma.
Cancer Immunol Res, 2014 Apr 30; 1(4). PMID: 24777852    Free PMC article.
Highly Cited.
Computational algorithm-driven evaluation of monocytic myeloid-derived suppressor cell frequency for prediction of clinical outcomes.
Shigehisa Kitano, Michael A Postow, +10 authors, Alexander M Lesokhin.
Cancer Immunol Res, 2014 May 23; 2(8). PMID: 24844912    Free PMC article.
Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients.
Edward Cha, Mark Klinger, +4 authors, Lawrence Fong.
Sci Transl Med, 2014 May 30; 6(238). PMID: 24871131    Free PMC article.
Highly Cited.
Interferon receptor signaling in malignancy: a network of cellular pathways defining biological outcomes.
Eleanor N Fish, Leonidas C Platanias.
Mol Cancer Res, 2014 Sep 14; 12(12). PMID: 25217450    Free PMC article.
Review.
Genetic basis for clinical response to CTLA-4 blockade in melanoma.
Alexandra Snyder, Vladimir Makarov, +18 authors, Timothy A Chan.
N Engl J Med, 2014 Nov 20; 371(23). PMID: 25409260    Free PMC article.
Highly Cited.
The IPD and IMGT/HLA database: allele variant databases.
James Robinson, Jason A Halliwell, +3 authors, Steven G E Marsh.
Nucleic Acids Res, 2014 Nov 22; 43(Database issue). PMID: 25414341    Free PMC article.
Highly Cited.
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer.
Thomas Powles, Joseph Paul Eder, +12 authors, Nicholas J Vogelzang.
Nature, 2014 Nov 28; 515(7528). PMID: 25428503
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.
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.
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.
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.
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.
Nivolumab and ipilimumab versus ipilimumab in untreated melanoma.
Michael A Postow, Jason Chesney, +18 authors, F Stephen Hodi.
N Engl J Med, 2015 Apr 22; 372(21). PMID: 25891304    Free PMC article.
Highly Cited.
Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients.
Emanuela Romano, Monika Kusio-Kobialka, +7 authors, Daniel E Speiser.
Proc Natl Acad Sci U S A, 2015 Apr 29; 112(19). PMID: 25918390    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.
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.
Peripheral T cell receptor diversity is associated with clinical outcomes following ipilimumab treatment in metastatic melanoma.
Michael A Postow, Manuarii Manuel, +9 authors, Jedd D Wolchok.
J Immunother Cancer, 2015 Jun 19; 3. PMID: 26085931    Free PMC article.
Highly Cited.
Genomic correlates of response to CTLA-4 blockade in metastatic melanoma.
Eliezer M Van Allen, Diana Miao, +19 authors, Levi A Garraway.
Science, 2015 Sep 12; 350(6257). PMID: 26359337    Free PMC article.
Highly Cited.
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.
Robert J Motzer, Bernard Escudier, +25 authors, CheckMate 025 Investigators.
N Engl J Med, 2015 Sep 26; 373(19). PMID: 26406148    Free PMC article.
Highly Cited.
Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.
Ayelet Sivan, Leticia Corrales, +9 authors, Thomas F Gajewski.
Science, 2015 Nov 07; 350(6264). PMID: 26541606    Free PMC article.
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.
Control of PD-L1 Expression by Oncogenic Activation of the AKT-mTOR Pathway in Non-Small Cell Lung Cancer.
Kristin J Lastwika, Willie Wilson, +10 authors, Phillip A Dennis.
Cancer Res, 2015 Dec 08; 76(2). PMID: 26637667
Highly Cited.
Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.
Krista Dubin, Margaret K Callahan, +9 authors, Jedd D Wolchok.
Nat Commun, 2016 Feb 03; 7. PMID: 26837003    Free PMC article.
Highly Cited.
Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade.
Nicholas McGranahan, Andrew J S Furness, +33 authors, Charles Swanton.
Science, 2016 Mar 05; 351(6280). PMID: 26940869    Free PMC article.
Highly Cited.
MYC regulates the antitumor immune response through CD47 and PD-L1.
Stephanie C Casey, Ling Tong, +8 authors, Dean W Felsher.
Science, 2016 Mar 12; 352(6282). PMID: 26966191    Free PMC article.
Highly Cited.
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.
Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability.
Bernhard Mlecnik, Gabriela Bindea, +29 authors, Jérôme Galon.
Immunity, 2016 Mar 18; 44(3). PMID: 26982367
Highly Cited.
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma.
Willy Hugo, Jesse M Zaretsky, +15 authors, Roger S Lo.
Cell, 2016 Mar 22; 165(1). PMID: 26997480    Free PMC article.
Highly Cited.
CANCER IMMUNOLOGY. The "cancer immunogram".
Christian U Blank, John B Haanen, Antoni Ribas, Ton N Schumacher.
Science, 2016 May 07; 352(6286). PMID: 27151852
Highly Cited.
Increases in Absolute Lymphocytes and Circulating CD4+ and CD8+ T Cells Are Associated with Positive Clinical Outcome of Melanoma Patients Treated with Ipilimumab.
Alexander Martens, Kilian Wistuba-Hamprecht, +15 authors, Benjamin Weide.
Clin Cancer Res, 2016 May 14; 22(19). PMID: 27169993    Free PMC article.
Highly Cited.
Targeting myeloid-derived suppressor cells with colony stimulating factor-1 receptor blockade can reverse immune resistance to immunotherapy in indoleamine 2,3-dioxygenase-expressing tumors.
Rikke B Holmgaard, Dmitriy Zamarin, +2 authors, Jedd D Wolchok.
EBioMedicine, 2016 May 24; 6. PMID: 27211548    Free PMC article.
Highly Cited.
Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers.
Keisuke Kataoka, Yuichi Shiraishi, +41 authors, Seishi Ogawa.
Nature, 2016 Jun 10; 534(7607). PMID: 27281199
Highly Cited.
Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade.
Pei-Ling Chen, Whijae Roh, +41 authors, Jennifer A Wargo.
Cancer Discov, 2016 Jun 16; 6(8). PMID: 27301722    Free PMC article.
Highly Cited.
Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma.
Jesse M Zaretsky, Angel Garcia-Diaz, +26 authors, Antoni Ribas.
N Engl J Med, 2016 Jul 20; 375(9). PMID: 27433843    Free PMC article.
Highly Cited.
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.
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.
Martin Reck, Delvys Rodríguez-Abreu, +16 authors, KEYNOTE-024 Investigators.
N Engl J Med, 2016 Oct 11; 375(19). PMID: 27718847
Highly Cited.
Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells.
Olivier De Henau, Matthew Rausch, +21 authors, Taha Merghoub.
Nature, 2016 Nov 10; 539(7629). PMID: 27828943    Free PMC article.
Highly Cited.
Density of immunogenic antigens does not explain the presence or absence of the T-cell-inflamed tumor microenvironment in melanoma.
Stefani Spranger, Jason J Luke, +6 authors, Thomas F Gajewski.
Proc Natl Acad Sci U S A, 2016 Nov 12; 113(48). PMID: 27837020    Free PMC article.
Highly Cited.
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.
PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project.
Fred R Hirsch, Abigail McElhinny, +19 authors, Keith M Kerr.
J Thorac Oncol, 2016 Dec 04; 12(2). PMID: 27913228
Highly Cited.
Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial.
Achim Rittmeyer, Fabrice Barlesi, +23 authors, OAK Study Group.
Lancet, 2016 Dec 17; 389(10066). PMID: 27979383    Free PMC article.
Highly Cited.
Immune Toxicities Elicted by CTLA-4 Blockade in Cancer Patients Are Associated with Early Diversification of the T-cell Repertoire.
David Y Oh, Jason Cham, +5 authors, Lawrence Fong.
Cancer Res, 2016 Dec 30; 77(6). PMID: 28031229    Free PMC article.
Potential Predictive Value of TP53 and KRAS Mutation Status for Response to PD-1 Blockade Immunotherapy in Lung Adenocarcinoma.
Zhong-Yi Dong, Wen-Zhao Zhong, +16 authors, Yi-Long Wu.
Clin Cancer Res, 2017 Jan 01; 23(12). PMID: 28039262
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.
Neutrophil to Lymphocyte Ratio is Associated With Outcome During Ipilimumab Treatment.
Michael R Cassidy, Rachel E Wolchok, +5 authors, Charlotte Ariyan.
EBioMedicine, 2017 Mar 31; 18. PMID: 28356222    Free PMC article.
Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab.
N Chaput, P Lepage, +15 authors, F Carbonnel.
Ann Oncol, 2017 Apr 04; 28(6). PMID: 28368458
Highly Cited.
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.
T-cell invigoration to tumour burden ratio associated with anti-PD-1 response.
Alexander C Huang, Michael A Postow, +31 authors, E John Wherry.
Nature, 2017 Apr 12; 545(7652). PMID: 28397821    Free PMC article.
Highly Cited.
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.
Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions.
Antje Sucker, Fang Zhao, +20 authors, Annette Paschen.
Nat Commun, 2017 Jun 01; 8. PMID: 28561041    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.
Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis.
Samra Turajlic, Kevin Litchfield, +17 authors, Charles Swanton.
Lancet Oncol, 2017 Jul 12; 18(8). PMID: 28694034
Highly Cited.
In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target.
Robert T Manguso, Hans W Pope, +16 authors, W Nicholas Haining.
Nature, 2017 Jul 21; 547(7664). PMID: 28723893    Free PMC article.
Highly Cited.
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.
Identification of essential genes for cancer immunotherapy.
Shashank J Patel, Neville E Sanjana, +21 authors, Nicholas P Restifo.
Nature, 2017 Aug 08; 548(7669). PMID: 28783722    Free PMC article.
Highly Cited.
Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient.
Alejandro Jiménez-Sánchez, Danish Memon, +16 authors, Martin L Miller.
Cell, 2017 Aug 26; 170(5). PMID: 28841418    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.
Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.
Jedd D Wolchok, Vanna Chiarion-Sileni, +30 authors, James Larkin.
N Engl J Med, 2017 Sep 12; 377(14). PMID: 28889792    Free PMC article.
Highly Cited.
Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients.
Arthur E Frankel, Laura A Coughlin, +4 authors, Andrew Y Koh.
Neoplasia, 2017 Sep 20; 19(10). PMID: 28923537    Free PMC article.
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.
Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab.
Nadeem Riaz, Jonathan J Havel, +22 authors, Timothy A Chan.
Cell, 2017 Oct 17; 171(4). PMID: 29033130    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.
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.
V Gopalakrishnan, C N Spencer, +67 authors, J A Wargo.
Science, 2017 Nov 04; 359(6371). PMID: 29097493    Free PMC article.
Highly Cited.
Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.
Bertrand Routy, Emmanuelle Le Chatelier, +45 authors, Laurence Zitvogel.
Science, 2017 Nov 04; 359(6371). PMID: 29097494
Highly Cited.
Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution.
Nicholas McGranahan, Rachel Rosenthal, +9 authors, TRACERx Consortium.
Cell, 2017 Nov 07; 171(6). PMID: 29107330    Free PMC article.
Highly Cited.
PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis.
Tim Wartewig, Zsuzsanna Kurgyis, +9 authors, Jürgen Ruland.
Nature, 2017 Nov 17; 552(7683). PMID: 29143824    Free PMC article.
Highly Cited.
Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy.
Diego Chowell, Luc G T Morris, +17 authors, Timothy A Chan.
Science, 2017 Dec 09; 359(6375). PMID: 29217585    Free PMC article.
Highly Cited.
Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA.
Matthew A Coelho, Sophie de Carné Trécesson, +11 authors, Julian Downward.
Immunity, 2017 Dec 17; 47(6). PMID: 29246442    Free PMC article.
Highly Cited.
The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients.
Vyara Matson, Jessica Fessler, +5 authors, Thomas F Gajewski.
Science, 2018 Jan 06; 359(6371). PMID: 29302014    Free PMC article.
Highly Cited.
Increased diversity with reduced "diversity evenness" of tumor infiltrating T-cells for the successful cancer immunotherapy.
Akihiro Hosoi, Kazuyoshi Takeda, +10 authors, Kazuhiro Kakimi.
Sci Rep, 2018 Jan 20; 8(1). PMID: 29348598    Free PMC article.
Cancer immunotherapy in 2017: The breakthrough of the microbiota.
Guido Kroemer, Laurence Zitvogel.
Nat Rev Immunol, 2018 Jan 31; 18(2). PMID: 29379189
Highly Cited. Review.
Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma.
Margaretha G M Roemer, Robert A Redd, +26 authors, Margaret A Shipp.
J Clin Oncol, 2018 Feb 03; 36(10). PMID: 29394125    Free PMC article.
Highly Cited.
Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms.
Alessandro Prestipino, Alica J Emhardt, +46 authors, Robert Zeiser.
Sci Transl Med, 2018 Feb 23; 10(429). PMID: 29467301    Free PMC article.
Highly Cited.
Cancer immunotherapy using checkpoint blockade.
Antoni Ribas, Jedd D Wolchok.
Science, 2018 Mar 24; 359(6382). PMID: 29567705    Free PMC article.
Highly Cited. Review.
Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.
Frederick Arce Vargas, Andrew J S Furness, +32 authors, Sergio A Quezada.
Cancer Cell, 2018 Mar 27; 33(4). PMID: 29576375    Free PMC article.
Highly Cited.
The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy.
Vancheswaran Gopalakrishnan, Beth A Helmink, +2 authors, Jennifer A Wargo.
Cancer Cell, 2018 Apr 11; 33(4). PMID: 29634945    Free PMC article.
Highly Cited. Review.
Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies.
Roberta Zappasodi, Taha Merghoub, Jedd D Wolchok.
Cancer Cell, 2018 Apr 11; 33(4). PMID: 29634946    Free PMC article.
Highly Cited. Review.
Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden.
Matthew D Hellmann, Tudor-Eliade Ciuleanu, +21 authors, Luis Paz-Ares.
N Engl J Med, 2018 Apr 17; 378(22). PMID: 29658845    Free PMC article.
Highly Cited.
A phase 1 study of lirilumab (antibody against killer immunoglobulin-like receptor antibody KIR2D; IPH2102) in patients with solid tumors and hematologic malignancies.
Norbert Vey, Lionel Karlin, +11 authors, Anthony Gonçalves.
Oncotarget, 2018 May 01; 9(25). PMID: 29707140    Free PMC article.
Highly Cited.
International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study.
Franck Pagès, Bernhard Mlecnik, +96 authors, Jérôme Galon.
Lancet, 2018 May 15; 391(10135). PMID: 29754777
Highly Cited.
Rapid Progression of Adult T-Cell Leukemia-Lymphoma after PD-1 Inhibitor Therapy.
Lee Ratner, Thomas A Waldmann, Murali Janakiram, Jonathan E Brammer.
N Engl J Med, 2018 May 17; 378(20). PMID: 29768155
Highly Cited.
Non-conventional Inhibitory CD4+Foxp3-PD-1hi T Cells as a Biomarker of Immune Checkpoint Blockade Activity.
Roberta Zappasodi, Sadna Budhu, +13 authors, Jedd D Wolchok.
Cancer Cell, 2018 Jun 13; 33(6). PMID: 29894689    Free PMC article.
Highly Cited.
Complex pattern of immune evasion in MSI colorectal cancer.
Mine Ozcan, Jonas Janikovits, Magnus von Knebel Doeberitz, Matthias Kloor.
Oncoimmunology, 2018 Jun 15; 7(7). PMID: 29900056    Free PMC article.
Enhancement of antitumor immunity by CTLA-4 blockade.
D R Leach, M F Krummel, J P Allison.
Science, 1996 Mar 22; 271(5256). PMID: 8596936
Highly Cited.
The IFN gamma receptor: a paradigm for cytokine receptor signaling.
E A Bach, M Aguet, R D Schreiber.
Annu Rev Immunol, 1997 Jan 01; 15. PMID: 9143700
Highly Cited. Review.
Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches.
Dongkui Song, Thomas Powles, +3 authors, Yong-Jie Lu.
J Pathol, 2019 May 19; 249(2). PMID: 31102277    Free PMC article.
Review.
Lessons Learned from Checkpoint Blockade Targeting PD-1 in Multiple Myeloma.
Alexander M Lesokhin, Susan Bal, Ashraf Z Badros.
Cancer Immunol Res, 2019 Aug 03; 7(8). PMID: 31371317    Free PMC article.
Review.
Assessing the Magnitude of Immunogenic Cell Death Following Chemotherapy and Irradiation Reveals a New Strategy to Treat Pancreatic Cancer.
Jian Ye, Bradley N Mills, +8 authors, Scott A Gerber.
Cancer Immunol Res, 2019 Nov 14; 8(1). PMID: 31719057    Free PMC article.
In vitro assays for effector T cell functions and activity of immunomodulatory antibodies.
Roberta Zappasodi, Sadna Budhu, Mohsen Abu-Akeel, Taha Merghoub.
Methods Enzymol, 2020 Jan 18; 631. PMID: 31948562    Free PMC article.
The Landscape of Novel Therapeutics and Challenges in Glioblastoma Multiforme: Contemporary State and Future Directions.
Karam Khaddour, Tanner M Johanns, George Ansstas.
Pharmaceuticals (Basel), 2020 Nov 19; 13(11). PMID: 33202642    Free PMC article.
Review.
Combining Radiotherapy and Immunotherapy in Lung Cancer: Can We Expect Limitations Due to Altered Normal Tissue Toxicity?
Florian Wirsdörfer, Simone de Leve, Verena Jendrossek.
Int J Mol Sci, 2018 Dec 24; 20(1). PMID: 30577587    Free PMC article.
Review.
The Expression Patterns and Associated Clinical Parameters of Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 and Transmembrane and Immunoglobulin Domain Containing 2 in Oral Squamous Cell Carcinoma.
Yao Xiao, Hao Li, +4 authors, Zhi-Jun Sun.
Dis Markers, 2019 May 16; 2019. PMID: 31089395    Free PMC article.
The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment.
Maximilian Haist, Henner Stege, Stephan Grabbe, Matthias Bros.
Cancers (Basel), 2021 Jan 13; 13(2). PMID: 33430105    Free PMC article.
Review.
T cell-engaging therapies - BiTEs and beyond.
Maria-Elisabeth Goebeler, Ralf C Bargou.
Nat Rev Clin Oncol, 2020 Apr 04; 17(7). PMID: 32242094
Review.
Tissues and Tumor Microenvironment (TME) in 3D: Models to Shed Light on Immunosuppression in Cancer.
Teresa Ho, Rasha Msallam.
Cells, 2021 May 01; 10(4). PMID: 33917037    Free PMC article.
Review.
The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps.
Silvia Gitto, Ambra Natalini, Fabrizio Antonangeli, Francesca Di Rosa.
Front Immunol, 2021 Dec 07; 12. PMID: 34867987    Free PMC article.
Review.
Reactive Oxygen Species in Anticancer Immunity: A Double-Edged Sword.
Jie Wang, Ning Liu, +2 authors, Dongming Xing.
Front Bioeng Biotechnol, 2021 Dec 07; 9. PMID: 34869295    Free PMC article.
Review.
PD-L1 expression in megakaryocytes and its clinicopathological features in primary myelofibrosis patients.
Sze-Hwei Lee, Chien-Chin Lin, +8 authors, Hwei-Fang Tien.
J Pathol Clin Res, 2021 Sep 05; 8(1). PMID: 34480529    Free PMC article.
Epigenetic, Metabolic, and Immune Crosstalk in Germinal-Center-Derived B-Cell Lymphomas: Unveiling New Vulnerabilities for Rational Combination Therapies.
Inna Serganova, Sanjukta Chakraborty, +5 authors, Roberta Zappasodi.
Front Cell Dev Biol, 2022 Jan 25; 9. PMID: 35071240    Free PMC article.
Review.
A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance.
Alexander C Huang, Roberta Zappasodi.
Nat Immunol, 2022 Mar 05; 23(5). PMID: 35241833    Free PMC article.
Review.
LncRNA LNCOC1 is Upregulated in Melanoma and Serves as a Potential Regulatory Target of miR-124 to Suppress Cancer Cell Invasion and Migration.
Changhai Liu, Xiangsheng Ding, +4 authors, Yi Liu.
Clin Cosmet Investig Dermatol, 2022 May 04; 15. PMID: 35502349    Free PMC article.
Novel Tracers and Radionuclides in PET Imaging.
Christian Mason, Grayson R Gimblet, Suzanne E Lapi, Jason S Lewis.
Radiol Clin North Am, 2021 Aug 17; 59(5). PMID: 34392925    Free PMC article.
Review.