The ectonucleotidase CD39 identifies tumor-reactive CD8+T cells predictive of immune checkpoint blockade efficacy in human lung cancer

被引：63

作者：

Chow, Andrew ^{[1
,2
,3
]}

Uddin, Fathema Z. ^{[1
]}

Liu, Michael ^{[1
]}

Dobrin, Anton ^{[4
,5
]}

Nabet, Barzin Y. ^{[6
]}

Mangarin, Levi ^{[2
]}

Lavin, Yonit ^{[1
]}

Rizvi, Hira ^{[7
]}

Tischfield, Sam E. ^{[8
]}

Quintanal-Villalonga, Alvaro ^{[1
]}

Chan, Joseph M. ^{[1
]}

Shah, Nisargbhai ^{[1
]}

Allaj, Viola ^{[1
]}

Manoj, Parvathy ^{[1
]}

Mattar, Marissa ^{[9
]}

Meneses, Maximiliano ^{[9
]}

Landau, Rebecca ^{[9
]}

Ward, Mariana ^{[9
]}

Kulick, Amanda ^{[9
]}

Kwong, Charlene ^{[9
]}

Wierzbicki, Matthew ^{[9
]}

Yavner, Jessica ^{[9
]}

Egger, Jacklynn ^{[7
]}

Chavan, Shweta S. ^{[8
]}

Farillas, Abigail ^{[1
]}

Holland, Aliya ^{[2
]}

Sridhar, Harsha ^{[1
]}

Ciampricotti, Metamia ^{[1
]}

Hirschhorn, Daniel ^{[2
]}

Guan, Xiangnan ^{[6
]}

Richards, Allison L. ^{[8
]}

Heller, Glenn ^{[10
]}

Mansilla-Soto, Jorge ^{[4
]}

Sadelain, Michel ^{[3
,4
]}

Klebanoff, Christopher A. ^{[3
,4
,11
,12
,13
]}

Hellmann, Matthew D. ^{[1
,3
,13
,15
]}

Sen, Triparna ^{[1
,16
]}

de Stanchina, Elisa

Wolchok, Jedd D. ^{[2
,3
,12
,13
,17
]}

Merghoub, Taha ^{[2
,3
,12
,13
,17
]}

Rudin, Charles M. ^{[1
,3
,7
,14
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Ludwig Collaborat & Swim Amer Lab, New York, NY 10065 USA

[3] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA

[4] Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, New York, NY USA

[5] Mem Sloan Kettering Canc Ctr, Louis V Gerstner Jr Grad Sch Biomed Sci, New York, NY USA

[6] Genentech Inc, Dept Oncol Biomarker Dev, South San Francisco, CA USA

[7] Mem Sloan Kettering Canc Ctr, Druckenmiler Ctr Lung Canc Res, New York, NY 10065 USA

[8] Mem Sloan Kettering Canc Ctr, Marie Josee & Henry R Kravis Ctr Mol Oncol, New York, NY USA

[9] Mem Sloan Kettering Canc Ctr, Antitumor Assessment Core, New York, NY USA

[10] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA

[11] Mem Sloan Kettering Canc Ctr, Dept Med, Breast Med Serv, New York, NY USA

[12] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[13] Parker Inst Canc Immunotherapy, Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA

[14] Mem Sloan Kettering Canc Ctr, Mol Pharmacol Program, New York, NY 10065 USA

[15] Astra Zeneca, Oncol R&D, Wilmington, DE USA

[16] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY USA

[17] Weill Cornell Med, Sandra & Edward Meyer Canc Ctr, New York, NY 10065 USA

来源：

IMMUNITY | 2023年 / 56卷 / 01期

关键词：

T-CELLS; PERIPHERAL-BLOOD; IMMUNOTHERAPY; MEDIATE; MODELS;

D O I：

10.1016/j.immuni.2022.12.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Improved identification of anti-tumor T cells is needed to advance cancer immunotherapies. CD39 expres-sion is a promising surrogate of tumor-reactive CD8+ T cells. Here, we comprehensively profiled CD39 expression in human lung cancer. CD39 expression enriched for CD8+ T cells with features of exhaustion, tumor reactivity, and clonal expansion. Flow cytometry of 440 lung cancer biospecimens revealed weak association between CD39+ CD8+ T cells and tumoral features, such as programmed death-ligand (PD-L1), tumor mutation burden, and driver mutations. Immune checkpoint blockade (ICB), but not cyto-toxic chemotherapy, increased intratumoral CD39+ CD8+ T cells. Higher baseline frequency of CD39+ CD8+ T cells conferred improved clinical outcomes from ICB therapy. Furthermore, a gene signature CD39+ CD8+ T cells predicted benefit from ICB, but not chemotherapy, in a phase III clinical trial of non small cell lung cancer. These findings highlight CD39 as a proxy of tumor-reactive CD8+ T cells in human lung cancer.

引用

页码：93 / +

页数：21

共 59 条

[1] Conserved pan-cancer microenvironment subtypes predict response to immunotherapy [J].

Bagaev, Alexander ;

Kotlov, Nikita ;

Nomie, Krystle ;

Svekolkin, Viktor ;

Gafurov, Azamat ;

Isaeva, Olga ;

Osokin, Nikita ;

Kozlov, Ivan ;

Frenkel, Felix ;

Gancharova, Olga ;

Almog, Nava ;

Tsiper, Maria ;

Ataullakhanov, Ravshan ;

Fowler, Nathan .

CANCER CELL, 2021, 39 (06) :845-+

[2] An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer [J].

Burr, Marian L. ;

Sparbier, Christina E. ;

Chan, Kah Lok ;

Chan, Yih-Chih ;

Kersbergen, Ariena ;

Lam, Enid Y. N. ;

Azidis-Yates, Elizabeth ;

Vassiliadis, Dane ;

Bell, Charles C. ;

Gilan, Omer ;

Jackson, Susan ;

Tan, Lavinia ;

Wong, Stephen Q. ;

Hollizeck, Sebastian ;

Michalak, Ewa M. ;

Siddle, Hannah, V ;

McCabe, Michael T. ;

Prinjha, Rab K. ;

Guerra, Glen R. ;

Solomon, Benjamin J. ;

Sandhu, Shahneen ;

Dawson, Sarah-Jane ;

Beavis, Paul A. ;

Tothill, Richard W. ;

Cullinane, Carleen ;

Lehner, Paul J. ;

Sutherland, Kate D. ;

Dawson, Mark A. .

CANCER CELL, 2019, 36 (04) :385-+

[3] Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers [J].

Caushi, Justina X. ;

Zhang, Jiajia ;

Ji, Zhicheng ;

Vaghasia, Ajay ;

Zhang, Boyang ;

Hsiue, Emily Han-Chung ;

Mog, Brian J. ;

Hou, Wenpin ;

Justesen, Sune ;

Blosser, Richard ;

Tam, Ada ;

Anagnostou, Valsamo ;

Cottrell, Tricia R. ;

Guo, Haidan ;

Chan, Hok Yee ;

Singh, Dipika ;

Thapa, Sampriti ;

Dykema, Arbor G. ;

Burman, Poromendro ;

Choudhury, Begum ;

Aparicio, Luis ;

Cheung, Laurene S. ;

Lanis, Mara ;

Belcaid, Zineb ;

El Asmar, Margueritta ;

Illei, Peter B. ;

Wang, Rulin ;

Meyers, Jennifer ;

Schuebel, Kornel ;

Gupta, Anuj ;

Skaist, Alyza ;

Wheelan, Sarah ;

Naidoo, Jarushka ;

Marrone, Kristen A. ;

Brock, Malcolm ;

Ha, Jinny ;

Bush, Errol L. ;

Park, Bernard J. ;

Bott, Matthew ;

Jones, David R. ;

Reuss, Joshua E. ;

Velculescu, Victor E. ;

Chaft, Jamie E. ;

Kinzler, Kenneth W. ;

Zhou, Shibin ;

Vogelstein, Bert ;

Taube, Janis M. ;

Hellmann, Matthew D. ;

Brahmer, Julie R. ;

Merghoub, Taha .

NATURE, 2021, 596 (7870) :126-+

[4]

Chakravarty Debyani, 2017, JCO Precis Oncol, V2017, DOI 10.1200/PO.17.00011

[5] Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers [J].

Chalabi, Myriam ;

Fanchi, Lorenzo F. ;

Dijkstra, Krijn K. ;

Van den Berg, Jose G. ;

Aalbers, Arend G. ;

Sikorska, Karolina ;

Lopez-Yurda, Marta ;

Grootscholten, Cecile ;

Beets, Geerard L. ;

Snaebjornsson, Petur ;

Maas, Monique ;

Mertz, Marjolijn ;

Veninga, Vivien ;

Bounova, Gergana ;

Broeks, Annegien ;

Beets-Tan, Regina G. ;

de Wijkerslooth, Thomas R. ;

van Lent, Anja U. ;

Marsman, Hendrik A. ;

Nuijten, Elvira ;

Kok, Niels F. ;

Kuiper, Maria ;

Verbeek, Wieke H. ;

Kok, Marleen ;

Van Leerdam, Monique E. ;

Schumacher, Ton N. ;

Voest, Emile E. ;

Haanen, John B. .

NATURE MEDICINE, 2020, 26 (04) :566-+

[6] Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity [J].

Chow, Andrew ;

Schad, Sara ;

Green, Michael D. ;

Hellmann, Matthew D. ;

Allaj, Viola ;

Ceglia, Nicholas ;

Zago, Giulia ;

Shah, Nisargbhai S. ;

Sharma, Sai Kiran ;

Mattar, Marissa ;

Chan, Joseph ;

Rizvi, Hira ;

Zhong, Hong ;

Liu, Cailian ;

Bykov, Yonina ;

Zamarin, Dmitriy ;

Shi, Hongyu ;

Budhu, Sadna ;

Wohlhieter, Corrin ;

Uddin, Fathema ;

Gupta, Aditi ;

Khodos, Inna ;

Waninger, Jessica J. ;

Qin, Angel ;

Markowitz, Geoffrey J. ;

Mittal, Vivek ;

Balachandran, Vinod ;

Durham, Jennifer N. ;

Le, Dung T. ;

Zou, Weiping ;

Shah, Sohrab P. ;

McPherson, Andrew ;

Panageas, Katherine ;

Lewis, Jason S. ;

Perry, Justin S. A. ;

de Stanchina, Elisa ;

Sen, Triparna ;

Poirier, John T. ;

Wolchok, Jedd D. ;

Rudin, Charles M. ;

Merghoub, Taha .

CANCER CELL, 2021, 39 (07) :973-+

[7] Evolutionary divergence of HLA class I genotype impacts efficacy of cancer immunotherapy [J].

Chowell, Diego ;

Krishna, Chirag ;

Pierini, Federica ;

Makarov, Vladimir ;

Rizvi, Naiyer A. ;

Kuo, Fengshen ;

Morris, Luc G. T. ;

Riaz, Nadeem ;

Lenz, Tobias L. ;

Chan, Timothy A. .

NATURE MEDICINE, 2019, 25 (11) :1715-+

[8] Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy [J].

Chowell, Diego ;

Morris, Luc G. T. ;

Grigg, Claud M. ;

Weber, Jeffrey K. ;

Samstein, Robert M. ;

Makarov, Vladimir ;

Kuo, Fengshen ;

Kendall, Sviatoslav M. ;

Requena, David ;

Riaz, Nadeem ;

Greenbaum, Benjamin ;

Carroll, James ;

Garon, Edward ;

Hyman, David M. ;

Zehir, Ahmet ;

Solit, David ;

Berger, Michael ;

Zhou, Ruhong ;

Rizvi, Naiyer A. ;

Chan, Timothy A. .

SCIENCE, 2018, 359 (6375) :582-+

[9] The Mutation-Associated Neoantigen Functional Expansion of Specific T Cells (MANAFEST) Assay: A Sensitive Platform for Monitoring Antitumor Immunity [J].

Danilova, Ludmila ;

Anagnostou, Valsamo ;

Caushi, Justina X. ;

Sidhom, John-William ;

Guo, Haidan ;

Chan, Hok Yee ;

Suri, Prerna ;

Tam, Ada ;

Zhang, Jiajia ;

El Asmar, Margueritta ;

Marrone, Kristen A. ;

Naidoo, Jarushka ;

Brahmer, Julie R. ;

Forde, Patrick M. ;

Baras, Alexander S. ;

Cope, Leslie ;

Velculescu, Victor E. ;

Pardoll, Drew M. ;

Housseau, Franck ;

Smith, Kellie N. .

CANCER IMMUNOLOGY RESEARCH, 2018, 6 (08) :888-899

[10] Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors [J].

Das, Satya ;

Johnson, Douglas B. .

JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2019, 7 (01)

← 1 2 3 4 5 6 →