Pan-cancer proteogenomics characterization of tumor immunity

Clinical Proteomic Tumor Analysis Consortium, Francesca Petralia, Weiping Ma, Tomer M. Yaron, Francesca Pia Caruso, Nicole Tignor, Joshua M. Wang, Daniel Charytonowicz, Jared L. Johnson, Emily M. Huntsman, Giacomo B. Marino, Anna Calinawan, John Erol Evangelista, Myvizhi Esai Selvan, Shrabanti Chowdhury, Dmitry Rykunov, Azra Krek, Xiaoyu Song, Berk Turhan, Karen E. ChristiansonDavid A. Lewis, Eden Z. Deng, Daniel J.B. Clarke, Jeffrey R. Whiteaker, Jacob J. Kennedy, Lei Zhao, Rossana Lazcano Segura, Harsh Batra, Maria Gabriela Raso, Edwin Roger Parra, Rama Soundararajan, Ximing Tang, Yize Li, Xinpei Yi, Shankha Satpathy, Ying Wang, Maciej Wiznerowicz, Tania J. González-Robles, Antonio Iavarone, Sara J.C. Gosline, Boris Reva, Ana I. Robles, Alexey I. Nesvizhskii, D. R. Mani, Michael A. Gillette, Robert J. Klein, Marcin Cieslik, Bing Zhang, Amanda G. Paulovich, Robert Sebra, Zeynep H. Gümüş, Galen Hostetter, David Fenyö, Gilbert S. Omenn, Lewis C. Cantley, Avi Ma'ayan, Alexander J. Lazar, Michele Ceccarelli, Pei Wang, Jennifer Abelin, François Aguet, Yo Akiyama, Eunkyung An, Shankara Anand, Meenakshi Anurag, Özgün Babur, Jasmin Bavarva, Chet Birger, Michael J. Birrer, Song Cao, Steven A. Carr, Daniel W. Chan, Arul M. Chinnaiyan, Hanbyul Cho, Karl Clauser, Antonio Colaprico, Daniel Cui Zhou, Felipe da Veiga Leprevost, Corbin Day, Saravana M. Dhanasekaran, Li Ding, Marcin J. Domagalski, Yongchao Dou, Brian J. Druker, Nathan Edwards, Matthew J. Ellis, Steven M. Foltz, Alicia Francis, Yifat Geffen, Gad Getz, David I. Heiman, Runyu Hong, Yingwei Hu, Chen Huang, Eric J. Jaehnig, Scott D. Jewell, Jiayi Ji, Wen Jiang, Lizabeth Katsnelson, Karen A. Ketchum, Iga Kolodziejczak, Karsten Krug, Chandan Kumar-Sinha, Jonathan T. Lei, Wen Wei Liang, Yuxing Liao, Caleb M. Lindgren, Tao Liu, Wenke Liu, Jason McDermott, Wilson McKerrow, Mehdi Mesri, Michael Brodie Mumphrey, Chelsea J. Newton, Robert Oldroyd, Samuel H. Payne, Pietro Pugliese, Karin D. Rodland, Fernanda Martins Rodrigues, Kelly V. Ruggles, Sara R. Savage, Eric E. Schadt, Michael Schnaubelt, Tobias Schraink, Stephan Schürer, Zhiao Shi, Richard D. Smith, Feng Song, Yizhe Song, Vasileios Stathias, Erik P. Storrs, Jimin Tan, Nadezhda V. Terekhanova, Ratna R. Thangudu, Mathangi Thiagarajan, Liang Bo Wang, Bo Wen, Yige Wu, Matthew A. Wyczalkowski, Lijun Yao, Qing Kay Li, Hui Zhang, Qing Zhang, Xu Zhang, Zhen Zhang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%–20% cancer cases have demonstrated durable responses from immune checkpoint blockade. To enhance the efficacy of immunotherapies, combination therapies suppressing multiple immune evasion mechanisms are increasingly contemplated. To better understand immune cell surveillance and diverse immune evasion responses in tumor tissues, we comprehensively characterized the immune landscape of more than 1,000 tumors across ten different cancers using CPTAC pan-cancer proteogenomic data. We identified seven distinct immune subtypes based on integrative learning of cell type compositions and pathway activities. We then thoroughly categorized unique genomic, epigenetic, transcriptomic, and proteomic changes associated with each subtype. Further leveraging the deep phosphoproteomic data, we studied kinase activities in different immune subtypes, which revealed potential subtype-specific therapeutic targets. Insights from this work will facilitate the development of future immunotherapy strategies and enhance precision targeting with existing agents.

Original languageEnglish
Pages (from-to)1255-1277.e27
JournalCell
Volume187
Issue number5
DOIs
StatePublished - Feb 29 2024

Keywords

  • histopathology
  • immune subtype
  • immunotherapy
  • kinase activity
  • multiomic deconvolution
  • proteogenomics
  • tumor immunity

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