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Pan-cancer proteogenomics characterization of tumor immunity.


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.

SUBMITTER: Petralia F 

PROVIDER: S-EPMC10988632 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Pan-cancer proteogenomics characterization of tumor immunity.

Petralia Francesca F   Ma Weiping W   Yaron Tomer M TM   Caruso Francesca Pia FP   Tignor Nicole N   Wang Joshua M JM   Charytonowicz Daniel D   Johnson Jared L JL   Huntsman Emily M EM   Marino Giacomo B GB   Calinawan Anna A   Evangelista John Erol JE   Selvan Myvizhi Esai ME   Chowdhury Shrabanti S   Rykunov Dmitry D   Krek Azra A   Song Xiaoyu X   Turhan Berk B   Christianson Karen E KE   Lewis David A DA   Deng Eden Z EZ   Clarke Daniel J B DJB   Whiteaker Jeffrey R JR   Kennedy Jacob J JJ   Zhao Lei L   Segura Rossana Lazcano RL   Batra Harsh H   Raso Maria Gabriela MG   Parra Edwin Roger ER   Soundararajan Rama R   Tang Ximing X   Li Yize Y   Yi Xinpei X   Satpathy Shankha S   Wang Ying Y   Wiznerowicz Maciej M   González-Robles Tania J TJ   Iavarone Antonio A   Gosline Sara J C SJC   Reva Boris B   Robles Ana I AI   Nesvizhskii Alexey I AI   Mani D R DR   Gillette Michael A MA   Klein Robert J RJ   Cieslik Marcin M   Zhang Bing B   Paulovich Amanda G AG   Sebra Robert R   Gümüş Zeynep H ZH   Hostetter Galen G   Fenyö David D   Omenn Gilbert S GS   Cantley Lewis C LC   Ma'ayan Avi A   Lazar Alexander J AJ   Ceccarelli Michele M   Wang Pei P  

Cell 20240214 5


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 t  ...[more]

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