Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy

被引：644

作者：

Gide, Tuba N. ^{[1
,2
]}

Quek, Camelia ^{[1
,2
]}

Menzies, Alexander M. ^{[1
,2
,3
,4
]}

Tasker, Annie T. ^{[1
]}

Shang, Ping ^{[1
]}

Holst, Jeff ^{[2
,5
]}

Madore, Jason ^{[1
]}

Lim, Su Yin ^{[1
,6
]}

Velickovic, Rebecca ^{[1
]}

Wongchenko, Matthew ^{[7
]}

Yan, Yibing ^{[7
]}

Lo, Serigne ^{[1
]}

Carlino, Matteo S. ^{[1
,2
,8
,9
]}

Guminski, Alexander ^{[1
,2
,3
,4
]}

Saw, Robyn P. M. ^{[1
,2
,10
]}

Pang, Angel ^{[2
,5
]}

McGuire, Helen M. ^{[11
,12
]}

Palendira, Umaimainthan ^{[2
,5
]}

Thompson, John F. ^{[1
,2
,10
]}

Rizos, Helen ^{[1
,6
]}

da Silva, Ines Pires ^{[1
,2
]}

Batten, Marcel ^{[1
,2
]}

Scolyer, Richard A. ^{[1
,2
,10
]}

Long, Georgina V. ^{[1
,2
,3
,4
]}

Wilmott, James S. ^{[1
,2
]}

机构：

[1] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2065, Australia

[2] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia

[3] Royal North Shore Hosp, Dept Med Oncol, Sydney, NSW 2065, Australia

[4] Mater Hosp, Dept Med Oncol, Sydney, NSW 2060, Australia

[5] Univ Sydney, Centenary Inst, Sydney, NSW 2050, Australia

[6] Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW 2109, Australia

[7] Genentech Inc, Oncol Biomarker Dev, San Francisco, CA 94080 USA

[8] Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW 2145, Australia

[9] Blacktown Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW 2145, Australia

[10] Royal Prince Alfred Hosp, Sydney, NSW 2050, Australia

[11] Univ Sydney, Charles Perkins Ctr, Ramaciotti Facil Human Syst Biol, Sydney, NSW 2006, Australia

[12] Univ Sydney, Fac Med & Hlth, Sch Med Sci, Discipline Pathol, Sydney, NSW 2006, Australia

来源：

CANCER CELL | 2019年 / 35卷 / 02期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

CARBONIC-ANHYDRASE IX; CD8; T-CELLS; INDOLEAMINE 2,3-DIOXYGENASE; CTLA-4; BLOCKADE; INHIBITORY RECEPTORS; COMBINATION THERAPY; CLINICAL-RESPONSE; PD-L1; EXPRESSION; DENDRITIC CELLS; MASS-CYTOMETRY;

D O I：

10.1016/j.ccell.2019.01.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancer immunotherapies provide survival benefits in responding patients, but many patients fail to respond. Identifying the biology of treatment response and resistance are a priority to optimize drug selection and improve patient outcomes. We performed transcriptomic and immune profiling on 158 tumor biopsies from melanoma patients treated with anti-PD-1 monotherapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57). These data identified activated T cell signatures and T cell populations in responders to both treatments. Further mass cytometry analysis identified an EOMES(+)CD69(+)CD45RO(+) effector memory T cell phenotype that was significantly more abundant in responders to combined immunotherapy compared with non-responders (n = 18). The gene expression profile of this population was associated with longer progression-free survival in patients treated with single agent and greater tumor shrinkage in both treatments.

引用

页码：238 / +

页数：24

共 84 条

[1] HTSeq-a Python']Python framework to work with high-throughput sequencing data
Anders, Simon
Pyl, Paul Theodor
Huber, Wolfgang
[J]. BIOINFORMATICS, 2015, 31 (02) : 166 - 169
[2] CD137 Is Expressed in Follicular Dendritic Cell Tumors and in Classical Hodgkin and T-Cell Lymphomas Diagnostic and Therapeutic Implications
Anderson, Matthew W.
Zhao, Shuchun
Freud, Aharon G.
Czerwinski, Debra K.
Kohrt, Holbrook
Alizadeh, Ash A.
Houot, Roch
Azambuja, Denize
Biasoli, Irene
Morais, Jose Carlos
Spector, Nelson
Molina-Kirsch, Hernan F.
Warnke, Roger A.
Levy, Ronald
Natkunam, Yasodha
[J]. AMERICAN JOURNAL OF PATHOLOGY, 2012, 181 (03) : 795 - 803
[3] The Intratumoral Balance between Metabolic and Immunologic Gene Expression Is Associated with Anti-PD-1 Response in Patients with Renal Cell Carcinoma
Ascierto, Maria Libera
McMiller, Tracee L.
Berger, Alan E.
Danilova, Ludmila
Anders, Robert A.
Netto, George J.
Xu, Haiying
Pritchard, Theresa S.
Fan, Jinshui
Cheadle, Chris
Cope, Leslie
Drake, Charles G.
Pardoll, Drew M.
Taube, Janis M.
Topalian, Suzanne L.
[J]. CANCER IMMUNOLOGY RESEARCH, 2016, 4 (09) : 726 - 733
[4] IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade
Ayers, Mark
Lunceford, Jared
Nebozhyn, Michael
Murphy, Erin
Loboda, Andrey
Kaufman, David R.
Albright, Andrew
Cheng, Jonathan D.
Kang, S. Peter
Shankaran, Veena
Piha-Paul, Sarina A.
Yearley, Jennifer
Seiwert, Tanguy Y.
Ribas, Antoni
McClanahan, Terrill K.
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2017, 127 (08) : 2930 - 2940
[5] 4-1 BB agonists: multi-potent potentiators of tumor immunity
Bartkowiak, Todd
Curran, Michael A.
[J]. FRONTIERS IN ONCOLOGY, 2015, 5
[6] Single-Cell Mass Cytometry of Differential Immune and Drug Responses Across a Human Hematopoietic Continuum
Bendall, Sean C.
Simonds, Erin F.
Qiu, Peng
Amir, El-ad D.
Krutzik, Peter O.
Finck, Rachel
Bruggner, Robert V.
Melamed, Rachel
Trejo, Angelica
Ornatsky, Olga I.
Balderas, Robert S.
Plevritis, Sylvia K.
Sachs, Karen
Pe'er, Dana
Tanner, Scott D.
Nolan, Garry P.
[J]. SCIENCE, 2011, 332 (6030) : 687 - 696
[7] Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection
Blackburn, Shawn D.
Shin, Haina
Haining, W. Nicholas
Zou, Tao
Workman, Creg J.
Polley, Antonio
Betts, Michael R.
Freeman, Gordon J.
Vignali, Dario A. A.
Wherry, E. John
[J]. NATURE IMMUNOLOGY, 2009, 10 (01) : 29 - 37
[8] Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockade
Blackburn, Shawn D.
Shin, Haina
Freeman, Gordon J.
Wherry, E. John
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (39) : 15016 - 15021
[9] Trimmomatic: a flexible trimmer for Illumina sequence data
Bolger, Anthony M.
Lohse, Marc
Usadel, Bjoern
[J]. BIOINFORMATICS, 2014, 30 (15) : 2114 - 2120
[10] Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer
Brahmer, Julie
Reckamp, Karen L.
Baas, Paul
Crino, Lucio
Eberhardt, Wilfried E. E.
Poddubskaya, Elena
Antonia, Scott
Pluzanski, Adam
Vokes, Everett E.
Holgado, Esther
Waterhouse, David
Ready, Neal
Gainor, Justin
Aren Frontera, Osvaldo
Havel, Libor
Steins, Martin
Garassino, Marina C.
Aerts, Joachim G.
Domine, Manuel
Paz-Ares, Luis
Reck, Martin
Baudelet, Christine
Harbison, Christopher T.
Lestini, Brian
Spigel, David R.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) : 123 - 135

← 1 2 3 4 5 6 7 8 9 →