Title | Pan-cancer proteogenomics characterization of tumor immunity. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Petralia 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 Authors | Clinical Proteomic Tumor Analysis Consortium |
Journal | Cell |
Volume | 187 |
Issue | 5 |
Pagination | 1255-1277.e27 |
Date Published | 2024 Feb 29 |
ISSN | 1097-4172 |
Keywords | Combined 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. |
DOI | 10.1016/j.cell.2024.01.027 |
Alternate Journal | Cell |
PubMed ID | 38359819 |
Grant List | U01 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 |