Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade

被引：3871

作者：

Charoentong, Pornpimol ^{[1
]}

Finotello, Francesca ^{[1
]}

Angelova, Mihaela ^{[1
]}

Mayer, Clemens ^{[1
]}

Efremova, Mirjana ^{[1
]}

Rieder, Dietmar ^{[1
]}

Hackl, Hubert ^{[1
]}

Trajanoski, Zlatko ^{[1
]}

机构：

[1] Med Univ Innsbruck, Div Bioinformat, Bioctr, A-6020 Innsbruck, Austria

来源：

CELL REPORTS | 2017年 / 18卷 / 01期

基金：

奥地利科学基金会; 欧盟地平线“2020”;

关键词：

IMMUNE CELLS; TUMOR; HETEROGENEITY; NEOANTIGENS; SENSITIVITY; MECHANISMS; IPILIMUMAB; MUTATIONS; LANDSCAPE; EVOLUTION;

D O I：

10.1016/j.celrep.2016.12.019

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming the treatment of advanced cancers. Unfortunately, the majority of patients do not respond to immunotherapy, making the identification of predictive markers and the mechanisms of resistance an area of intense research. To increase our understanding of tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers and created The Cancer Immunome Atlas (https://tcia.at/). Cellular characterization of the immune infiltrates showed that tumor genotypes determine immunophenotypes and tumor escape mechanisms. Using machine learning, we identified determinants of tumor immunogenicity and developed a scoring scheme for the quantification termed immunophenoscore. The immunophenoscore was a superior predictor of response to anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) and anti-programmed cell death protein 1 (anti-PD-1) antibodies in two independent validation cohorts. Our findings and this resource may help inform cancer immunotherapy and facilitate the development of precision immuno-oncology.

引用

页码：248 / 262

页数：15

共 39 条

[1]

Integrated Genomic Characterization of Papillary Thyroid Carcinoma [J].

Agrawal, Nishant ;

Akbani, Rehan ;

Aksoy, B. Arman ;

Ally, Adrian ;

Arachchi, Harindra ;

Asa, Sylvia L. ;

Auman, J. Todd ;

Balasundaram, Miruna ;

Balu, Saianand ;

Baylin, Stephen B. ;

Behera, Madhusmita ;

Bernard, Brady ;

Beroukhim, Rameen ;

Bishop, Justin A. ;

Black, Aaron D. ;

Bodenheimer, Tom ;

Boice, Lori ;

Bootwalla, Moiz S. ;

Bowen, Jay ;

Bowlby, Reanne ;

Bristow, Christopher A. ;

Brookens, Robin ;

Brooks, Denise ;

Bryant, Robert ;

Buda, Elizabeth ;

Butterfield, Yaron S. N. ;

Carling, Tobias ;

Carlsen, Rebecca ;

Carter, Scott L. ;

Carty, Sally E. ;

Chan, Timothy A. ;

Chen, Amy Y. ;

Cherniack, Andrew D. ;

Cheung, Dorothy ;

Chin, Lynda ;

Cho, Juok ;

Chu, Andy ;

Chuah, Eric ;

Cibulskis, Kristian ;

Ciriello, Giovanni ;

Clarke, Amanda ;

Clayman, Gary L. ;

Cope, Leslie ;

Copland, John A. ;

Covington, Kyle ;

Danilova, Ludmila ;

Davidsen, Tanja ;

Demchok, John A. ;

DiCara, Daniel ;

Dhalla, Noreen .

CELL, 2014, 159 (03) :676-690

[2]

Genomic Classification of Cutaneous Melanoma [J].

Akbani, Rehan ;

Akdemir, Kadir C. ;

Aksoy, B. Arman ;

Albert, Monique ;

Ally, Adrian ;

Amin, Samirkumar B. ;

Arachchi, Harindra ;

Arora, Arshi ;

Auman, J. Todd ;

Ayala, Brenda ;

Baboud, Julien ;

Balasundaram, Miruna ;

Balu, Saianand ;

Barnabas, Nandita ;

Bartlett, John ;

Bartlett, Pam ;

Bastian, Boris C. ;

Baylin, Stephen B. ;

Behera, Madhusmita ;

Belyaev, Dmitry ;

Benz, Christopher ;

Bernard, Brady ;

Beroukhim, Rameen ;

Bir, Natalie ;

Black, Aaron D. ;

Bodenheimer, Tom ;

Boice, Lori ;

Boland, Genevieve M. ;

Bono, Riccardo ;

Bootwalla, Moiz S. ;

Bosenberg, Marcus ;

Bowen, Jay ;

Bowlby, Reanne ;

Bristow, Christopher A. ;

Brockway-Lunardi, Laura ;

Brooks, Denise ;

Brzezinski, Jakub ;

Bshara, Wiam ;

Buda, Elizabeth ;

Burns, William R. ;

Butterfield, Yaron S. N. ;

Button, Michael ;

Calderone, Tiffany ;

Cappellini, Giancarlo Antonini ;

Carter, Candace ;

Carter, Scott L. ;

Cherney, Lynn ;

Cherniack, Andrew D. ;

Chevalier, Aaron ;

Chin, Lynda .

CELL, 2015, 161 (07) :1681-1696

[3]

Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy [J].

Angelova, Mihaela ;

Charoentong, Pornpimol ;

Hackl, Hubert ;

Fischer, Maria L. ;

Snajder, Rene ;

Krogsdam, Anne M. ;

Waldner, Maximilian J. ;

Bindea, Gabriela ;

Mlecnik, Bernhard ;

Galon, Jerome ;

Trajanoski, Zlatko .

GENOME BIOLOGY, 2015, 16

[4]

Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 [J].

Barbie, David A. ;

Tamayo, Pablo ;

Boehm, Jesse S. ;

Kim, So Young ;

Moody, Susan E. ;

Dunn, Ian F. ;

Schinzel, Anna C. ;

Sandy, Peter ;

Meylan, Etienne ;

Scholl, Claudia ;

Froehling, Stefan ;

Chan, Edmond M. ;

Sos, Martin L. ;

Michel, Kathrin ;

Mermel, Craig ;

Silver, Serena J. ;

Weir, Barbara A. ;

Reiling, Jan H. ;

Sheng, Qing ;

Gupta, Piyush B. ;

Wadlow, Raymond C. ;

Le, Hanh ;

Hoersch, Sebastian ;

Wittner, Ben S. ;

Ramaswamy, Sridhar ;

Livingston, David M. ;

Sabatini, David M. ;

Meyerson, Matthew ;

Thomas, Roman K. ;

Lander, Eric S. ;

Mesirov, Jill P. ;

Root, David E. ;

Gilliland, D. Gary ;

Jacks, Tyler ;

Hahn, William C. .

NATURE, 2009, 462 (7269) :108-U122

[5]

Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer [J].

Bindea, Gabriela ;

Mlecnik, Bernhard ;

Tosolini, Marie ;

Kirilovsky, Amos ;

Waldner, Maximilian ;

Obenauf, Anna C. ;

Angell, Helen ;

Fredriksen, Tessa ;

Lafontaine, Lucie ;

Berger, Anne ;

Bruneval, Patrick ;

Fridman, Wolf Herman ;

Becker, Christoph ;

Pages, Franck ;

Speicher, Michael R. ;

Trajanoski, Zlatko ;

Galon, Jerome .

IMMUNITY, 2013, 39 (04) :782-795

[6]

ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks [J].

Bindea, Gabriela ;

Mlecnik, Bernhard ;

Hackl, Hubert ;

Charoentong, Pornpimol ;

Tosolini, Marie ;

Kirilovsky, Amos ;

Fridman, Wolf-Herman ;

Pages, Franck ;

Trajanoski, Zlatko ;

Galon, Jerome .

BIOINFORMATICS, 2009, 25 (08) :1091-1093

[7]

The "cancer immunogram" [J].

Blank, Christian U. ;

Haanen, John B. ;

Ribas, Antoni ;

Schumacher, Ton N. .

SCIENCE, 2016, 352 (6286) :658-660

[8]

Random forests [J].

Breiman, L .

MACHINE LEARNING, 2001, 45 (01) :5-32

[9]

Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival [J].

Brown, Scott D. ;

Warren, Rene L. ;

Gibb, Ewan A. ;

Martin, Spencer D. ;

Spinelli, John J. ;

Nelson, Brad H. ;

Holt, Robert A. .

GENOME RESEARCH, 2014, 24 (05) :743-750

[10]

Antitumor activity of epigenetic immunomodulation combined with CTLA-4 blockade in syngeneic mouse models [J].

Covre, A. ;

Coral, S. ;

Nicolay, H. ;

Parisi, G. ;

Fazio, C. ;

Colizzi, F. ;

Fratta, E. ;

Di Giacomo, A. M. ;

Sigalotti, L. ;

Natali, P. G. ;

Maio, M. .

ONCOIMMUNOLOGY, 2015, 4 (08)

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