Open AccessMedicineBiology

V. Thorsson, David L. Gibbs, S. Brown, D. Wolf, Dante S. Bortone, T. Yang, Eduard Porta-Pardo, G. Gao, Christopher L. Plaisier, James A. Eddy, E. Ziv, A. Culhane, Evan O. Paull, A. Sivakumar, A. Gentles, R. Malhotra, F. Farshidfar, A. Colaprico, J. Parker, Lisle E. Mose, N. Vo, Jianfang Liu, Yuexin Liu, J. Rader, Varsha Dhankani, Sheila M. Reynolds, R. Bowlby, A. Califano, A. Cherniack, D. Anastassiou, D. Bedognetti, A. Rao, Ken Chen, A. Krasnitz, Hai Hu, T. Malta, H. Noushmehr, C. Pedamallu, S. Bullman, A. Ojesina, Andrew Lamb, Wanding Zhou, Hui Shen, T. Choueiri, J. Weinstein, J. Guinney, J. Saltz, R. Holt, Charles E. Rabkin, Samantha J. Caesar-Johnson, J. Demchok, Ina Felau, M. Kasapi, M. Ferguson, C. Hutter, H. Sofia, R. Tarnuzzer, Zhining Wang, Liming Yang, J. Zenklusen, Jiashan Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, R. Naresh, T. Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, T. DeFreitas, S. Frazer, Nils Gehlenborg, G. Getz, David I Heiman, Jaegil Kim, M. Lawrence, Pei Lin, S. Meier, M. Noble, G. Saksena, D. Voet, Hailei Zhang, Brady Bernard, N. Chambwe, T. Knijnenburg, R. Kramer, Kalle Leinonen, Michael Miller, Sheila M. Reynolds, I. Shmulevich, V. Thorsson, Wei Zhang, Rehan Akbani, B. Broom, A. Hegde, Z. Ju, R. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, G. Mills, Kwok-shing Ng, Michael J. Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, J. Armenia, D. Chakravarty, W. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, R. Kundra, Konnor C. La, M. Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, F. Sánchez-Vega, C. Sander, N. Schultz, R. Sheridan, O. Sumer, Yichao Sun, B. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, P. Spellman, C. Benz, Joshua M. Stuart, Christopher K. Wong, C. Yau, N. Hayes, M. Wilkerson, Adrian Ally, M. Balasundaram, Denise Brooks, R. Carlsen, E. Chuah, Noreen Dhalla, R. Holt, Steven J. M. Jones, K. Kasaian, Darlene Lee, Yussanne Ma, M. Marra, Michael Mayo, Richard A. Moore, A. Mungall, K. Mungall, Gordon Robertson, S. Sadeghi, J. Schein, Payal Sipahimalani, Angela Tam, N. Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, R. Beroukhim, C. Cibulskis, S. Gabriel, G. Ha, M. Meyerson, S. Schumacher, J. Shih, M. Kucherlapati, R. Kucherlapati, S. Baylin, Ludmila V. Danilova, M. Bootwalla, Phillip H. Lai, D. Maglinte, D. J. Van Den Berg, D. Weisenberger, T. Auman, S. Balu, T. Bodenheimer, C. Fan, K. Hoadley, A. Hoyle, S. Jefferys, Corbin D. Jones, S. Meng, P. Mieczkowski, Amy H. Perou, C. Perou, J. Roach, Yan Shi, J. Simons, Tara J. Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, T. Hinoue, P. Laird, Michelle Bellair, Kyle Chang, K. Covington, C. Creighton, H. Dinh, H. Doddapaneni, L. Donehower, J. Drummond, R. Gibbs, R. Glenn, Walker Hale, Yi Han, Jianhong Hu, V. Korchina, Sandy Lee, L. Lewis, Wei Li, Xiuping Liu, M. Morgan, Donna Morton, D. Muzny, J. Santibanez, Margi Sheth, E. Shinbrot, Linghua Wang, Min Wang, D. Wheeler, Liu Xi, Fengmei Zhao, J. Hess, Elizabeth L. Appelbaum, Matthew H. Bailey, M. Cordes, L. Ding, Catrina C. Fronick, L. Fulton, R. Fulton, Cyriac Kandoth, E. Mardis, M. McLellan, Christopher A. Miller, Heather K. Schmidt, R. Wilson, D. Crain, Erin E. Curley, J. Gardner, Kevin R Lau, D. Mallery, S. Morris, J. Paulauskis, R. Penny, C. Shelton, T. Shelton, M. Sherman, E. Thompson, P. Yena, Jay Bowen, J. Gastier-Foster, M. Gerken, K. Leraas, T. Lichtenberg, N. Ramirez, L. Wise, E. Zmuda, N. Corcoran, T. Costello, C. Hovens, A. Carvalho, A. C. de Carvalho, J. Fregnani, A. Longatto-Filho, R. Reis, C. Scapulatempo-Neto, H. C. Silveira, D. O. Vidal, Andrew Burnette, J. Eschbacher, B. Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, M. Ittmann, D. Huntsman, B. Kohl, X. Le, Richard A. Thorp, C. Andry, Elizabeth R. Duffy, V. Lyadov, O. Paklina, G. Setdikova, A. Shabunin, M. Tavobilov, Christopher M. McPherson, R. Warnick, R. Berkowitz, Daniel Cramer, C. Feltmate, Neil Horowitz, A. Kibel, M. Muto, C. Raut, A. Malykh, J. Barnholtz-Sloan, Wendi Barrett, K. Devine, J. Fulop, Q. Ostrom, K. Shimmel, Yingli Wolinsky, A. Sloan, A. D. De Rose, F. Giuliante, M. Goodman, B. Karlan, C. Hagedorn, J. Eckman, Jodi Harr, J. Myers, Kelinda Tucker, L. A. Zach, B. Deyarmin, L. Kvecher, C. Larson, R. Mural, S. Somiari, A. Vícha, T. Zelinka, J. Bennett, M. Iacocca, B. Rabeno, P. Swanson, M. Latour, L. Lacombe, B. Têtu, A. Bergeron, Mary McGraw, S. Staugaitis, J. Chabot, H. Hibshoosh, A. Sepulveda, T. Su, Timothy C. Wang, O. Potapova, Olga Voronina, L. Desjardins, O. Mariani, S. Roman-Roman, X. Sastre, M. Stern, F. Cheng, S. Signoretti, A. Berchuck, D. Bigner, E. Lipp, J. Marks, S. McCall, R. McLendon, A. Secord, A. Sharp, M. Behera, D. Brat, Amy Y. Chen, K. Delman, S. Force, F. Khuri, K. Magliocca, S. Maithel, J. Olson, T. Owonikoko, A. Pickens, S. Ramalingam, Dong-Myung Shin, G. Sica, Erwin G. Van Meir, Hongzhen Zhang, Wil Eijckenboom, A. Gillis, E. Korpershoek, L. Looijenga, W. Oosterhuis, H. Stoop, K. V. van Kessel, E. Zwarthoff, C. Calatozzolo, L. Cuppini, S. Cuzzubbo, F. DiMeco, G. Finocchiaro, L. Mattei, A. Perin, B. Pollo, Chu Chen, J. Houck, Pawadee Lohavanichbutr, A. Hartmann, C. Stoehr, R. Stoehr, H. Taubert, S. Wach, B. Wullich, W. Kycler, D. Murawa, M. Wiznerowicz, K. Chung, J. Edenfield, Julie M Martin, E. Baudin, G. Bubley, R. Bueno, A. De Rienzo, W. Richards, S. Kalkanis, T. Mikkelsen, L. Scarpace, N. Girard, M. Aymerich, E. Campo, E. Giné, A. Guillermo, Nguyen Van Bang, Phan Thi Hong Hanh, Bui Duc Phu, Yufang Tang, H. Colman, Kimberley J. Evason, P. Dottino, J. Martignetti, H. Gabra, H. Juhl, Teniola Akeredolu, Serghei Stepa, D. Hoon, K. Ahn, K. Kang, F. Beuschlein, A. Breggia, M. Birrer, D. Bell, M. Borad, A. Bryce, E. Castle, V. Chandan, J. Cheville, J. Copland, M. Farnell, T. Flotte, N. Giama, T. Ho, M. Kendrick, J. Kocher, Karla J. Kopp, C. Moser, D. Nagorney, Daniel R. O'Brien, B. O’Neill, T. Patel, G. Petersen, F. Que, M. Rivera, L. Roberts, R. Smallridge, T. Smyrk, M. Stanton, H. Thompson, M. Torbenson, J. D. Yang, Lizhi Zhang, F. Brimo, J. Ajani, A. Gonzalez, C. Behrens, J. Bondaruk, R. Broaddus, B. Czerniak, B. Esmaeli, J. Fujimoto, J. Gershenwald, Charles C. Guo, C. Logothetis, F. Meric-Bernstam, C. Moran, L. Ramondetta, D. Rice, A. Sood, P. Tamboli, T. Thompson, P. Troncoso, A. Tsao, I. Wistuba, Candace D. Carter, L. Haydu, P. Hersey, V. Jakrot

2018.4.5Immunity

DOI: 10.1016/j.immuni.2018.03.023

tlooto Summary

An extensive immunogenomic analysis of over 10,000 tumors comprising 33 diverse cancer types utilizing data compiled by TCGA identified six immune subtypes, characterized by differences in macrophage or lymphocyte signatures, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis.

Abstract

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field.

Citation format

THORSSON, V., et al. The immune landscape of cancer. Immunity, 2018, 48: 812–830.e14.