Englander Institute for Precision Medicine

Pan-cancer proteogenomics characterization of tumor immunity.

TitlePan-cancer proteogenomics characterization of tumor immunity.
Publication TypeJournal Article
Year of Publication2024
AuthorsPetralia F, Ma W, Yaron TM, Caruso FPia, Tignor N, Wang JM, Charytonowicz D, Johnson JL, Huntsman EM, Marino GB, Calinawan A, Evangelista JErol, Selvan MEsai, Chowdhury S, Rykunov D, Krek A, Song X, Turhan B, Christianson KE, Lewis DA, Deng EZ, Clarke DJB, Whiteaker JR, Kennedy JJ, Zhao L, Segura RLazcano, Batra H, Raso MGabriela, Parra ERoger, Soundararajan R, Tang X, Li Y, Yi X, Satpathy S, Wang Y, Wiznerowicz M, González-Robles TJ, Iavarone A, Gosline SJC, Reva B, Robles AI, Nesvizhskii AI, Mani DR, Gillette MA, Klein RJ, Cieslik M, Zhang B, Paulovich AG, Sebra R, Gümüş ZH, Hostetter G, Fenyö D, Omenn GS, Cantley LC, Ma'ayan A, Lazar AJ, Ceccarelli M, Wang P
Corporate AuthorsClinical Proteomic Tumor Analysis Consortium
JournalCell
Volume187
Issue5
Pagination1255-1277.e27
Date Published2024 Feb 29
ISSN1097-4172
KeywordsCombined Modality Therapy, Genomics, Humans, Neoplasms, Proteogenomics, Proteomics, Tumor Escape
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.

DOI10.1016/j.cell.2024.01.027
Alternate JournalCell
PubMed ID38359819
Grant ListU01 CA214116 / CA / NCI NIH HHS / United States
U24 CA210985 / CA / NCI NIH HHS / United States
U24 CA210967 / CA / NCI NIH HHS / United States
U24 CA210986 / CA / NCI NIH HHS / United States
U24 CA270823 / CA / NCI NIH HHS / United States
U24 CA210972 / CA / NCI NIH HHS / United States
U24 CA210955 / CA / NCI NIH HHS / United States
U24 CA210993 / CA / NCI NIH HHS / United States
U24 CA210979 / CA / NCI NIH HHS / United States
U24 CA271114 / CA / NCI NIH HHS / United States
U01 CA214114 / CA / NCI NIH HHS / United States
U01 CA214125 / CA / NCI NIH HHS / United States

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