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The Immune Landscape of Cancer
Thorsson V.11; Gibbs D.L.11; Brown S.D.23; Wolf D.21; Bortone D.S.16; Ou Yang T.-H.17; Porta-Pardo E.32; Gao G.F.12; Plaisier C.L.11; Eddy J.A.8; Ziv E.29; Culhane A.C.1; Paull E.O.4; Sivakumar I.K.A.19; Gentles A.J.26; Malhotra R.9; Farshidfar F.18; Colaprico A.25; Parker J.S.16; Mose L.E.16; Vo N.S.2; Liu J.6; Liu Y.2; Rader J.31; Dhankani V.11; Reynolds S.M.11; Bowlby R.23; Califano A.4; Cherniack A.D.12; Anastassiou D.17; Bedognetti D.5; Rao A.2; Chen K.2; Krasnitz A.14; Hu H.6; Malta T.M.30; Noushmehr H.30; Pedamallu C.S.1; Bullman S.1; Ojesina A.I.22; Lamb A.8; Zhou W.10; Shen H.10; Choueiri T.K.1; Weinstein J.N.2; Guinney J.8; Saltz J.7; Holt R.A.23; Rabkin C.E.13; Caesar-Johnson S.J.; Demchok J.A.; Felau I.; Kasapi M.; Ferguson M.L.; Hutter C.M.; Sofia H.J.; Tarnuzzer R.; Wang Z.; Yang L.; Zenklusen J.C.; Zhang J.J.; Chudamani S.; Liu J.; Lolla L.; Naresh R.; Pihl T.; Sun Q.; Wan Y.; Wu Y.; Cho J.; DeFreitas T.; Frazer S.; Gehlenborg N.; Getz G.; Heiman D.I.; Kim J.; Lawrence M.S.; Lin P.; Meier S.; Noble M.S.; Saksena G.; Voet D.; Zhang H.; Bernard B.; Chambwe N.; Dhankani V.11; Knijnenburg T.; Kramer R.; Leinonen K.; Liu Y.; Miller M.; Reynolds S.; Shmulevich I.; Thorsson V.; Zhang W.; Akbani R.; Broom B.M.; Hegde A.M.; Ju Z.; Kanchi R.S.; Korkut A.; Li J.; Liang H.; Ling S.; Liu W.; Lu Y.; Mills G.B.; Ng K.-S.; Rao A.; Ryan M.; Wang J.; Weinstein J.N.; Zhang J.; Abeshouse A.; Armenia J.; Chakravarty D.; Chatila W.K.; de Bruijn I.; Gao J.; Gross B.E.; Heins Z.J.; Kundra R.; La K.; Ladanyi M.; Luna A.; Nissan M.G.; Ochoa A.; Phillips S.M.; Reznik E.; Sanchez-Vega F.; Sander C.; Schultz N.; Sheridan R.; Sumer S.O.; Sun Y.; Taylor B.S.; Wang J.; Zhang H.; Anur P.; Peto M.; Spellman P.; Benz C.; Stuart J.M.; Wong C.K.; Yau C.; Hayes D.N.; Parker J.S.; Wilkerson M.D.; Ally A.; Balasundaram M.; Bowlby R.; Brooks D.; Carlsen R.; Chuah E.; Dhalla N.; Holt R.; Jones S.J.M.; Kasaian K.; Lee D.; Ma Y.; Marra M.A.; Mayo M.; Moore R.A.; Mungall A.J.; Mungall K.; Robertson A.G.; Sadeghi S.; Schein J.E.; Sipahimalani P.; Tam A.; Thiessen N.; Tse K.; Wong T.; Berger A.C.; Beroukhim R.; Cherniack A.D.; Cibulskis C.; Gabriel S.B.; Gao G.F.; Ha G.; Meyerson M.; Schumacher S.E.; Shih J.; Kucherlapati M.H.; Kucherlapati R.S.; Baylin S.; Cope L.; Danilova L.; Bootwalla M.S.; Lai P.H.; Maglinte D.T.; Van Den Berg D.J.; Weisenberger D.J.; Auman J.T.; Balu S.; Bodenheimer T.; Fan C.; Hoadley K.A.; Hoyle A.P.; Jefferys S.R.; Jones C.D.; Meng S.; Mieczkowski P.A.; Mose L.E.16; Perou A.H.; Perou C.M.; Roach J.; Shi Y.; Simons J.V.; Skelly T.; Soloway M.G.; Tan D.; Veluvolu U.; Fan H.; Hinoue T.; Laird P.W.; Shen H.; Zhou W.; Bellair M.; Chang K.; Covington K.; Creighton C.J.; Dinh H.; Doddapaneni H.; Donehower L.A.; Drummond J.; Gibbs R.A.; Glenn R.; Hale W.; Han Y.; Hu J.; Korchina V.; Lee S.; Lewis L.; Li W.; Liu X.; Morgan M.; Morton D.; Muzny D.; Santibanez J.; Sheth M.; Shinbrot E.; Wang L.; Wang M.; Wheeler D.A.; Xi L.; Zhao F.; Hess J.; Appelbaum E.L.; Bailey M.; Cordes M.G.; Ding L.; Fronick C.C.; Fulton L.A.; Fulton R.S.; Kandoth C.; Mardis E.R.; McLellan M.D.; Miller C.A.; Schmidt H.K.; Wilson R.K.; Crain D.; Curley E.; Gardner J.; Lau K.; Mallery D.; Morris S.; Paulauskis J.; Penny R.; Shelton C.; Shelton T.; Sherman M.; Thompson E.; Yena P.; Bowen J.; Gastier-Foster J.M.; Gerken M.; Leraas K.M.; Lichtenberg T.M.; Ramirez N.C.; Wise L.; Zmuda E.; Corcoran N.; Costello T.; Hovens C.; Carvalho A.L.; de Carvalho A.C.; Fregnani J.H.; Longatto-Filho A.; Reis R.M.; Scapulatempo-Neto C.; Silveira H.C.S.; Vidal D.O.; Burnette A.; Eschbacher J.; Hermes B.; Noss A.; Singh R.; Anderson M.L.; Castro P.D.; Ittmann M.; Huntsman D.; Kohl B.; Le X.; Thorp R.; Andry C.; Duffy E.R.; Lyadov V.; Paklina O.; Setdikova G.; Shabunin A.; Tavobilov M.; McPherson C.; Warnick R.; Berkowitz R.; Cramer D.; Feltmate C.; Horowitz N.; Kibel A.; Muto M.; Raut C.P.; Malykh A.; Barnholtz-Sloan J.S.; Barrett W.; Devine K.; Fulop J.; Ostrom Q.T.; Shimmel K.; Wolinsky Y.; Sloan A.E.; De Rose A.; Giuliante F.; Goodman M.; Karlan B.Y.; Hagedorn C.H.; Eckman J.; Harr J.; Myers J.; Tucker K.; Zach L.A.; Deyarmin B.; Hu H.; Kvecher L.; Larson C.; Mural R.J.; Somiari S.; Vicha A.; Zelinka T.; Bennett J.; Iacocca M.; Rabeno B.; Swanson P.; Latour M.; Lacombe L.; Tetu B.; Bergeron A.; McGraw M.; Staugaitis S.M.; Chabot J.; Hibshoosh H.; Sepulveda A.; Su T.; Wang T.; Potapova O.; Voronina O.; Desjardins L.; Mariani O.; Roman-Roman S.; Sastre X.; Stern M.-H.; Cheng F.; Signoretti S.; Berchuck A.; Bigner D.; Lipp E.; Marks J.; McCall S.; McLendon R.; Secord A.; Sharp A.; Behera M.; Brat D.J.; Chen A.; Delman K.; Force S.; Khuri F.; Magliocca K.; Maithel S.; Olson J.J.; Owonikoko T.; Pickens A.; Ramalingam S.; Shin D.M.; Sica G.; Van Meir E.G.; Zhang H.; Eijckenboom W.; Gillis A.; Korpershoek E.; Looijenga L.; Oosterhuis W.; Stoop H.; van Kessel K.E.; Zwarthoff E.C.; Calatozzolo C.; Cuppini L.; Cuzzubbo S.; DiMeco F.; Finocchiaro G.; Mattei L.; Perin A.; Pollo B.; Chen C.; Houck J.; Lohavanichbutr P.; Hartmann A.; Stoehr C.; Stoehr R.; Taubert H.; Wach S.; Wullich B.; Kycler W.; Murawa D.; Wiznerowicz M.; Chung K.; Edenfield W.J.; Martin J.; Baudin E.; Bubley G.; Bueno R.; De Rienzo A.; Richards W.G.; Kalkanis S.; Mikkelsen T.; Noushmehr H.30; Scarpace L.; Girard N.; Aymerich M.; Campo E.; Gine E.; Guillermo A.L.; Van Bang N.; Hanh P.T.; Phu B.D.; Tang Y.; Colman H.; Evason K.; Dottino P.R.; Martignetti J.A.; Gabra H.; Juhl H.; Akeredolu T.; Stepa S.; Hoon D.; Ahn K.; Kang K.J.; Beuschlein F.; Breggia A.; Birrer M.; Bell D.; Borad M.; Bryce A.H.; Castle E.; Chandan V.; Cheville J.; Copland J.A.; Farnell M.; Flotte T.; Giama N.; Ho T.; Kendrick M.; Kocher J.-P.; Kopp K.; Moser C.; Nagorney D.; O'Brien D.; O'Neill B.P.; Patel T.; Petersen G.; Que F.; Rivera M.; Roberts L.; Smallridge R.; Smyrk T.; Stanton M.; Thompson R.H.; Torbenson M.; Yang J.D.; Zhang L.; Brimo F.; Ajani J.A.; Gonzalez A.M.A.; Behrens C.; Bondaruk J.; Broaddus R.; Czerniak B.; Esmaeli B.; Fujimoto J.; Gershenwald J.; Guo C.; Lazar A.J.; Logothetis C.; Meric-Bernstam F.; Moran C.; Ramondetta L.; Rice D.; Sood A.; Tamboli P.; Thompson T.; Troncoso P.; Tsao A.; Wistuba I.; Carter C.; Haydu L.; Hersey P.; Jakrot V.; Kakavand H.; Kefford R.; Lee K.; Long G.; Mann G.; Quinn M.; Saw R.; Scolyer R.; Shannon K.; Spillane A.; Stretch O.; Synott M.; Thompson J.; Wilmott J.; Al-Ahmadie H.; Chan T.A.; Ghossein R.; Gopalan A.; Levine D.A.; Reuter V.; Singer S.; Singh B.; Tien N.V.; Broudy T.; Mirsaidi C.; Nair P.; Drwiega P.; Miller J.; Smith J.; Zaren H.; Park J.-W.; Hung N.P.; Kebebew E.; Linehan W.M.; Metwalli A.R.; Pacak K.; Pinto P.A.; Schiffman M.; Schmidt L.S.; Vocke C.D.; Wentzensen N.; Worrell R.; Yang H.; Moncrieff M.; Goparaju C.; Melamed J.; Pass H.; Botnariuc N.; Caraman I.; Cernat M.; Chemencedji I.; Clipca A.; Doruc S.; Gorincioi G.; Mura S.; Pirtac M.; Stancul I.; Tcaciuc D.; Albert M.; Alexopoulou I.; Arnaout A.; Bartlett J.; Engel J.; Gilbert S.; Parfitt J.; Sekhon H.; Thomas G.; Rassl D.M.; Rintoul R.C.; Bifulco C.; Tamakawa R.; Urba W.; Hayward N.; Timmers H.; Antenucci A.; Facciolo F.; Grazi G.; Marino M.; Merola R.; de Krijger R.; Gimenez-Roqueplo A.-P.; Piche A.; Chevalier S.; McKercher G.; Birsoy K.; Barnett G.; Brewer C.; Farver C.; Naska T.; Pennell N.A.; Raymond D.; Schilero C.; Smolenski K.; Williams F.; Morrison C.; Borgia J.A.; Liptay M.J.; Pool M.; Seder C.W.; Junker K.; Omberg L.; Dinkin M.; Manikhas G.; Alvaro D.; Bragazzi M.C.; Cardinale V.; Carpino G.; Gaudio E.; Chesla D.; Cottingham S.; Dubina M.; Moiseenko F.; Dhanasekaran R.; Becker K.-F.; Janssen K.-P.; Slotta-Huspenina J.; Abdel-Rahman M.H.; Aziz D.; Bell S.; Cebulla C.M.; Davis A.; Duell R.; Elder J.B.; Hilty J.; Kumar B.; Lang J.; Lehman N.L.; Mandt R.; Nguyen P.; Pilarski R.; Rai K.; Schoenfield L.; Senecal K.; Wakely P.; Hansen P.; Lechan R.; Powers J.; Tischler A.; Grizzle W.E.; Sexton K.C.; Kastl A.; Henderson J.; Porten S.; Waldmann J.; Fassnacht M.; Asa S.L.; Schadendorf D.; Couce M.; Graefen M.; Huland H.; Sauter G.; Schlomm T.; Simon R.; Tennstedt P.; Olabode O.; Nelson M.; Bathe O.; Carroll P.R.; Chan J.M.; Disaia P.; Glenn P.; Kelley R.K.; Landen C.N.; Phillips J.; Prados M.; Simko J.; Smith-McCune K.; VandenBerg S.; Roggin K.; Fehrenbach A.; Kendler A.; Sifri S.; Steele R.; Jimeno A.; Carey F.; Forgie I.; Mannelli M.; Carney M.; Hernandez B.; Campos B.; Herold-Mende C.; Jungk C.; Unterberg A.; von Deimling A.; Bossler A.; Galbraith J.; Jacobus L.; Knudson M.; Knutson T.; Ma D.; Milhem M.; Sigmund R.; Godwin A.K.; Madan R.; Rosenthal H.G.; Adebamowo C.; Adebamowo S.N.; Boussioutas A.; Beer D.; Giordano T.; Mes-Masson A.-M.; Saad F.; Bocklage T.; Landrum L.; Mannel R.; Moore K.; Moxley K.; Postier R.; Walker J.; Zuna R.; Feldman M.; Valdivieso F.; Dhir R.; Luketich J.; Pinero E.M.M.; Quintero-Aguilo M.; Carlotti C.G.; Dos Santos J.S.; Kemp R.; Sankarankuty A.; Tirapelli D.; Catto J.; Agnew K.; Swisher E.; Creaney J.; Robinson B.; Shelley C.S.; Godwin E.M.; Kendall S.; Shipman C.; Bradford C.; Carey T.; Haddad A.; Moyer J.; Peterson L.; Prince M.; Rozek L.; Wolf G.; Bowman R.; Fong K.M.; Yang I.; Korst R.; Rathmell W.K.; Fantacone-Campbell J.L.; Hooke J.A.; Kovatich A.J.; Shriver C.D.; DiPersio J.; Drake B.; Govindan R.; Heath S.; Ley T.; Van Tine B.; Westervelt P.; Rubin M.A.; Lee J.I.; Aredes N.D.; Mariamidze A.; Lazar A.J.2; Serody J.S.28; Demicco E.G.27; Disis M.L.20; Vincent B.G.16; Shmulevich L.11
2018-04-17
Source PublicationImmunity
ISSN10974180 10747613
Volume48Issue:4Pages:812-830.e14
Abstract

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, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field. Thorsson et al. present immunogenomics analyses of more than 10,000 tumors, identifying six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis. This work provides a resource for understanding tumor-immune interactions, with implications for identifying ways to advance research on immunotherapy.

KeywordCancer Genomics Immune Subtypes Immuno-oncology Immunomodulatory Immunotherapy Integrative Network Analysis Tumor Immunology Tumor Microenvironment
DOI10.1016/j.immuni.2018.03.023
URLView the original
Language英語English
WOS IDWOS:000430198900025
Scopus ID2-s2.0-85044934017
Fulltext Access
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Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Dana-Farber Cancer Institute
2.University of Texas MD Anderson Cancer Center
3.SBP Medical Discovery Institute
4.Irving Cancer Research Center
5.Sidra Medical and Research Center
6.Chan Soon-Shiong Institute of Molecular Medicine at Windber
7.Stony Brook Medicine
8.Sage Bionetworks
9.Seven Bridges Genomics Inc.
10.Van Andel Research Institute
11.Institute for Systems Biology
12.Broad Institute
13.National Cancer Institute
14.Cold Spring Harbor Laboratory
15.Universidade de Sao Paulo - USP
16.The University of North Carolina at Chapel Hill
17.Columbia University in the City of New York
18.University of Calgary
19.Johns Hopkins University
20.University of Washington, Seattle
21.University of California, San Francisco
22.University of Alabama at Birmingham
23.British Columbia Cancer Agency
24.Arizona State University
25.Université libre de Bruxelles (ULB)
26.Stanford University
27.Mount Sinai Hospital of University of Toronto
28.UNC Health Care
29.UCSF Helen Diller Family Comprehensive Cancer Center
30.Henry Ford Hospital
31.Medical College of Wisconsin
32.Centro Nacional de Supercomputación
Recommended Citation
GB/T 7714
Thorsson V.,Gibbs D.L.,Brown S.D.,et al. The Immune Landscape of Cancer[J]. Immunity, 2018, 48(4), 812-830.e14.
APA Thorsson V.., Gibbs D.L.., Brown S.D.., Wolf D.., Bortone D.S.., Ou Yang T.-H.., Porta-Pardo E.., Gao G.F.., Plaisier C.L.., Eddy J.A.., Ziv E.., Culhane A.C.., Paull E.O.., Sivakumar I.K.A.., Gentles A.J.., Malhotra R.., Farshidfar F.., Colaprico A.., Parker J.S.., ...& Shmulevich L. (2018). The Immune Landscape of Cancer. Immunity, 48(4), 812-830.e14.
MLA Thorsson V.,et al."The Immune Landscape of Cancer".Immunity 48.4(2018):812-830.e14.
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