biostudies-literaturePetralia FAssociazione Italiana per la Ricerca sul CancroHoward Hughes Medical InstituteNIEHS NIH HHSNational Cancer InstituteNCI NIH HHSUS Department of DefenseNational Institutes of HealthNIGMS NIH HHS1255-1277.e27https://www.ebi.ac.uk/biostudies/studies/S-EPMC10988632biostudies-literatureUnknown187(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 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.CellPan-cancer proteogenomics characterization of tumor immunity.PMC10988632U24 CA264250U24 CA210967P30 ES017885U24 CA224260U24 CA210985U24 CA210986R33 CA263705U01 CA214125F30 CA265288HHSN261201500003IU24 CA270823R35 CA197588HHSN261201500003CT32 GM136542U24 CA210979F30 CA271622U24 CA210954U24 CA210955U01 CA214116U24 CA210972U24 CA210993U54 CA263001U24 CA271075U24 CA271114U01 CA214114T32 GM146636U24 CA271012Wyczalkowski MAAkiyama YHu YHuntsman EMZhang HJewell SDYaron TMShi ZZhang QSoundararajan RDou YRobles AILei JTSchraink TKatsnelson LZhang BNewton CJLi QKRaso MGSegura RLPaulovich AGRodland KDAn EEdwards NCarr SAMumphrey MBRykunov DSatpathy SStathias VFoltz SMKrug KNesvizhskii AIFenyo DTerekhanova NVKrek ACalinawan AYi XChan DWSmith RDSebra RAnurag MStorrs EPLewis DADruker BJMcKerrow WZhao LReva BMarino GBAguet FSchurer SWhiteaker JRTang XWang JMClauser KSelvan MEGumus ZHRuggles KVBavarva JChinnaiyan AMSchadt EEDay CBatra Hda Veiga Leprevost FCantley LCCao SAbelin JCieslik MHong RCaruso FPHuang CPayne SHCeccarelli MMcDermott JLindgren CMPugliese PColaprico AEvangelista JEBabur OWang LBWang PClarke DJBOmenn GSWen BWang YWu YYao LJohnson JLLiao YWiznerowicz MTan JFrancis AAnand STurhan BMa'ayan AThangudu RRKetchum KALi YBirger CHostetter GClinical Proteomic Tumor Analysis ConsortiumBirrer MJDhanasekaran SMKumar-Sinha CJaehnig EJCharytonowicz DLazar AJGeffen YDeng EZIavarone AGetz GChowdhury SLiang WWParra ERLiu TDing LMa WGosline SJCLiu WRodrigues FMGillette MAZhou DCCho HJiang WPetralia FThiagarajan MTignor NMani DRSong XChristianson KESong YKlein RJKennedy JJOldroyd RSavage SRDomagalski MJJi JSong FSchnaubelt MGonzalez-Robles TJZhang ZEllis MJZhang XHeiman DIKolodziejczak IMesri MfalsePan-cancer proteogenomics characterization of tumor immunity.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.2024-01-01T00:00:00Z2024 Feb2026-05-05T03:23:20.941Z2026-05-05T03:13:22.067ZS-EPMC109886323835981910.1016/j.cell.2024.01.027