biostudies-literatureThorsson VNCINIEHS NIH HHSNHGRI NIH HHSNCI NIH HHSNLM NIH HHSSeven Bridges Cancer Genomics CloudUS Department of DefenseInstitute for Systems Biology-Cancer Genomics CloudCancer Research InstituteNational Cancer Institute, NIH, Department of Health and Human ServicesNIH HHSNIGMS NIH HHS812-830.e14https://www.ebi.ac.uk/biostudies/studies/S-EPMC5982584biostudies-literatureUnknown48(4)We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAsImmunityThe Immune Landscape of Cancer.PMC5982584U24 CA143845U54 CA209997U24 CA143867U24 CA143848U54 HG003273R01 LM009239U24 CA210949U54 HG003079U24 CA210969U54 HG003067HU0001-16-2-0004R50 CA221675P30 CA016086K24 CA169004HHSN261201400008CW81XWH-12-2-0050U01 CA217858U24 CA143866U24 CA143843U24 CA143882U24 CA143840U24 CA143883R01 CA163722R01 CA184585U24 CA143835R35 CA197745U24 CA143858U54 HG003067S10 OD012351P20 GM130423P30 ES010126U24 CA210957P50 CA058223P30 CA016672U24 CA210950P30 CA045508U24 CA180924HHSN261201400007CU24 CA210990U24 CA143799U24 CA144025S10 OD021764Latour MSchadendorf DCreaney JPerou CMDrwiega PLyadov VDanilova LSchumacher SEVan Bang NDonehower LALawrence MSJimeno ABerger ACBathe OJunker KGlenn PKandoth CKnudson MGlenn RSchiffman MKendall SBrewer CHibshoosh HHegde AMChemencedji IWalker JMariamidze AMeric-Bernstam FGerken MHeath SZach LAMcLendon RCheville JHooke JAKemp 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JPiche ADeyarmin BThompson EJefferys SRCibulskis CBullman SBryce AHSander CJungk CChan TAChesla DAnastassiou DThorp RFarnell MBossler ALi JScarpace LLewis LLi WPaulauskis JHuntsman DCherniack ADTamakawa RFeltmate CStaugaitis SMWaldmann JBowman RGrazi GBerchuck ACastle ESood ARyan MRamalingam SJu ZCarlsen RSoloway MGHoon DArnaout AEckman JTaubert HRamondetta LOosterhuis WSimons JVHagedorn CHMorris SStanton MPark JWXi LDottino PRMiller CAHung NPRaymond DKendler AGodwin AKGehlenborg NOmberg LMalykh ABell DStancul IDesjardins Lvan Kessel KEHartmann ABalasundaram MSeder CWForce SChoueiri TKLipp EMurawa DDhanasekaran RZhang WLohavanichbutr PAlbert MMoore KShih JBell SGovindan RGuillermo ALClipca AKundra RLarson CSifri SThompson TShabunin AZhang JZhang HWheeler DAHouck JO'Brien DShelton TZhang LShi YVidal DOSetdikova GSanchez-Vega FLai PHPollo BBeuschlein FSepulveda AMartin JDuell RShriver CDSmolenski KHa GLinehan WMDe Rose AMariani OBrown SDCramer DHerold-Mende CLuketich JHayward NCreighton CJGrizzle WEWistuba IFarshidfar FHenderson JEschbacher JMannelli MFronick CCBroaddus RFassnacht MNaska TZuna RShelton CGuinney JGine ERice DLee SShipman CParker JSCancer Genome Atlas Research NetworkLee KSantibanez JEsmaeli BLevine DAKim JChuah ESekhon HLee DDiMeco FSherman MTien NVRintoul RCJanssen KPHolt RAEngel JJones SJMWakely PAbeshouse AStern MHTang YCheng FBarnett GSwanson PWilkerson MDKebebew EJones CDMcPherson CSastre XTorbenson MZhou WCorcoran NHarr JTam AGardner JUrba WDisaia PTaylor BSFong KMThiessen NMattei LSpillane ARabkin CSTarnuzzer RDinh HCaraman ILu YPedamallu CSHermes BPorta-Pardo EWang JSimon RSivakumar IKAWang LBrooks DWang MGiordano TPostier RPhillips SMSun QWilmott JWang TPhu BDKibel AColman HBorgia JAWang ZGillis AWu YYang HMungall AJYang IYang LKnutson TLogothetis CNaresh RTan DHinoue TPihl TSun YBenz CStepa SBodenheimer TGershenwald JSloan AELe XFehrenbach AHo TPool MLongatto-Filho AMuto MSaltz JKvecher LOjesina AIFrazer SBueno RVeluvolu ULazar AJLong GRobertson AGBellair MGabra HMcCall SCope LSheridan RPerou AHAuman JTDing LChakravarty DCarroll PRSheth MSchmidt HKSauter GDrake BKasapi MSchultz NGopalan APowers JWeinstein JNDoddapaneni HLanden CNHaydu LSica GKopp KKucherlapati RSDubina MForgie IAntenucci AWorrell RNguyen PYena PBergeron AZaren HBirsoy KChan JMKrasnitz AAlexopoulou IRader JHeiman DIReuter VBubley GRobinson BPennell NAKelley RKMorgan MKumar BRubin MAAdebamowo SNfalseThe Immune Landscape of Cancer.We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs2018-01-01T00:00:00Z2018 Apr2026-04-30T10:51:46Z2019-06-06T19:37:31ZS-EPMC59825842962829010.1016/j.immuni.2018.03.023