The Immune Landscape of Cancer

V. Thorsson; D. L. Gibbs; S. D. Brown; D. Wolf; D. S. Bortone; T. H. Ou Yang; E. Porta-Pardo; G. F. Gao; C. L. Plaisier; J. A. Eddy; E. Ziv; A. C. Culhane; E. O. Paull; I. K. A. Sivakumar; A. J. Gentles; R. Malhotra; F. Farshidfar; A. Colaprico; J. S. Parker; L. E. Mose; N. S. Vo; J. Liu; Y. Liu; J. Rader; V. Dhankani; S. M. Reynolds; R. Bowlby; A. Califano; A. D. Cherniack; D. Anastassiou; D. Bedognetti; A. Rao; K. Chen; A. Krasnitz; H. Hu; T. M. Malta; H. Noushmehr; C. S. Pedamallu; S. Bullman; A. I. Ojesina; A. Lamb; W. Zhou; H. Shen; T. K. Choueiri; J. N. Weinstein; J. Guinney; J. Saltz; R. A. Holt; C. E. Rabkin; Cancer Genome Atlas Research Network; A. J. Lazar; J. S. Serody; E. G. Demicco; M. L. Disis; B. G. Vincent; L. Shmulevich; M. (come contributors) Marino

doi:S1074-7613(18)30121-3 [pii]

The Immune Landscape of Cancer

V. Thorsson, D. L. Gibbs, S. D. Brown, D. Wolf, D. S. Bortone, T. H. Ou Yang, E. Porta-Pardo, G. F. Gao, C. L. Plaisier, J. A. Eddy, E. Ziv, A. C. Culhane, E. O. Paull, I. K. A. Sivakumar, A. J. Gentles, R. Malhotra, F. Farshidfar, A. Colaprico, J. S. Parker, L. E. MoseN. S. Vo, J. Liu, Y. Liu, J. Rader, V. Dhankani, S. M. Reynolds, R. Bowlby, A. Califano, A. D. Cherniack, D. Anastassiou, D. Bedognetti, A. Rao, K. Chen, A. Krasnitz, H. Hu, T. M. Malta, H. Noushmehr, C. S. Pedamallu, S. Bullman, A. I. Ojesina, A. Lamb, W. Zhou, H. Shen, T. K. Choueiri, J. N. Weinstein, J. Guinney, J. Saltz, R. A. Holt, C. E. Rabkin, Cancer Genome Atlas Research Network, A. J. Lazar, J. S. Serody, E. G. Demicco, M. L. Disis, B. G. Vincent, L. Shmulevich, M. (come contributors) Marino

Research output: Contribution to journal › Article › peer-review

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-gamma dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-beta 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.

Original language	English
Pages (from-to)	812-830.e14
Journal	Immunity
Volume	48
Issue number	4
DOIs	https://doi.org/S1074-7613(18)30121-3 [pii]
Publication status	Published - Apr 17 2018
Externally published	Yes

Keywords

cancer genomics
immune subtypes
immuno-oncology
immunomodulatory
immunotherapy
integrative network analysis
tumor immunology
tumor microenvironment

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Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Yang, T. H. O., 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., ... Marino, M. . C. (2018). The Immune Landscape of Cancer. Immunity, 48(4), 812-830.e14. https://doi.org/S1074-7613(18)30121-3 [pii]

The Immune Landscape of Cancer. / Thorsson, V.; Gibbs, D. L.; Brown, S. D.; Wolf, D.; Bortone, D. S.; Yang, T. H. Ou; 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.; Mose, L. E.; Vo, N. S.; Liu, J.; Liu, Y.; Rader, J.; Dhankani, V.; Reynolds, S. M.; Bowlby, R.; Califano, A.; Cherniack, A. D.; Anastassiou, D.; Bedognetti, D.; Rao, A.; Chen, K.; Krasnitz, A.; Hu, H.; Malta, T. M.; Noushmehr, H.; Pedamallu, C. S.; Bullman, S.; Ojesina, A. I.; Lamb, A.; Zhou, W.; Shen, H.; Choueiri, T. K.; Weinstein, J. N.; Guinney, J.; Saltz, J.; Holt, R. A.; Rabkin, C. E.; Network, Cancer Genome Atlas Research; Lazar, A. J.; Serody, J. S.; Demicco, E. G.; Disis, M. L.; Vincent, B. G.; Shmulevich, L.; Marino, M. (come contributors).

In: Immunity, Vol. 48, No. 4, 17.04.2018, p. 812-830.e14.

Research output: Contribution to journal › Article › peer-review

Thorsson, V, Gibbs, DL, Brown, SD, Wolf, D, Bortone, DS, Yang, THO, Porta-Pardo, E, Gao, GF, Plaisier, CL, Eddy, JA, Ziv, E, Culhane, AC, Paull, EO, Sivakumar, IKA, Gentles, AJ, Malhotra, R, Farshidfar, F, Colaprico, A, Parker, JS, Mose, LE, Vo, NS, Liu, J, Liu, Y, Rader, J, Dhankani, V, Reynolds, SM, Bowlby, R, Califano, A, Cherniack, AD, Anastassiou, D, Bedognetti, D, Rao, A, Chen, K, Krasnitz, A, Hu, H, Malta, TM, Noushmehr, H, Pedamallu, CS, Bullman, S, Ojesina, AI, Lamb, A, Zhou, W, Shen, H, Choueiri, TK, Weinstein, JN, Guinney, J, Saltz, J, Holt, RA, Rabkin, CE, Network, CGAR, Lazar, AJ, Serody, JS, Demicco, EG, Disis, ML, Vincent, BG, Shmulevich, L & Marino, MC 2018, 'The Immune Landscape of Cancer', Immunity, vol. 48, no. 4, pp. 812-830.e14. https://doi.org/S1074-7613(18)30121-3 [pii]

Thorsson, V. ; Gibbs, D. L. ; Brown, S. D. ; Wolf, D. ; Bortone, D. S. ; Yang, T. H. Ou ; 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. ; Mose, L. E. ; Vo, N. S. ; Liu, J. ; Liu, Y. ; Rader, J. ; Dhankani, V. ; Reynolds, S. M. ; Bowlby, R. ; Califano, A. ; Cherniack, A. D. ; Anastassiou, D. ; Bedognetti, D. ; Rao, A. ; Chen, K. ; Krasnitz, A. ; Hu, H. ; Malta, T. M. ; Noushmehr, H. ; Pedamallu, C. S. ; Bullman, S. ; Ojesina, A. I. ; Lamb, A. ; Zhou, W. ; Shen, H. ; Choueiri, T. K. ; Weinstein, J. N. ; Guinney, J. ; Saltz, J. ; Holt, R. A. ; Rabkin, C. E. ; Network, Cancer Genome Atlas Research ; Lazar, A. J. ; Serody, J. S. ; Demicco, E. G. ; Disis, M. L. ; Vincent, B. G. ; Shmulevich, L. ; Marino, M. (come contributors). / The Immune Landscape of Cancer. In: Immunity. 2018 ; Vol. 48, No. 4. pp. 812-830.e14.

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title = "The Immune Landscape of Cancer",

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-gamma dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-beta 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.",

keywords = "cancer genomics, immune subtypes, immuno-oncology, immunomodulatory, immunotherapy, integrative network analysis, tumor immunology, tumor microenvironment",

author = "V. Thorsson and Gibbs, {D. L.} and Brown, {S. D.} and D. Wolf and Bortone, {D. S.} and Yang, {T. H. Ou} and E. Porta-Pardo and Gao, {G. F.} and Plaisier, {C. L.} and Eddy, {J. A.} and E. Ziv and Culhane, {A. C.} and Paull, {E. O.} and Sivakumar, {I. K. A.} and Gentles, {A. J.} and R. Malhotra and F. Farshidfar and A. Colaprico and Parker, {J. S.} and Mose, {L. E.} and Vo, {N. S.} and J. Liu and Y. Liu and J. Rader and V. Dhankani and Reynolds, {S. M.} and R. Bowlby and A. Califano and Cherniack, {A. D.} and D. Anastassiou and D. Bedognetti and A. Rao and K. Chen and A. Krasnitz and H. Hu and Malta, {T. M.} and H. Noushmehr and Pedamallu, {C. S.} and S. Bullman and Ojesina, {A. I.} and A. Lamb and W. Zhou and H. Shen and Choueiri, {T. K.} and Weinstein, {J. N.} and J. Guinney and J. Saltz and Holt, {R. A.} and Rabkin, {C. E.} and Network, {Cancer Genome Atlas Research} and Lazar, {A. J.} and Serody, {J. S.} and Demicco, {E. G.} and Disis, {M. L.} and Vincent, {B. G.} and L. Shmulevich and Marino, {M. (come contributors)}",

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doi = "S1074-7613(18)30121-3 [pii]",

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pages = "812--830.e14",

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TY - JOUR

T1 - The Immune Landscape of Cancer

AU - Thorsson, V.

AU - Gibbs, D. L.

AU - Brown, S. D.

AU - Wolf, D.

AU - Bortone, D. S.

AU - Yang, T. H. Ou

AU - Porta-Pardo, E.

AU - Gao, G. F.

AU - Plaisier, C. L.

AU - Eddy, J. A.

AU - Ziv, E.

AU - Culhane, A. C.

AU - Paull, E. O.

AU - Sivakumar, I. K. A.

AU - Gentles, A. J.

AU - Malhotra, R.

AU - Farshidfar, F.

AU - Colaprico, A.

AU - Parker, J. S.

AU - Mose, L. E.

AU - Vo, N. S.

AU - Liu, J.

AU - Liu, Y.

AU - Rader, J.

AU - Dhankani, V.

AU - Reynolds, S. M.

AU - Bowlby, R.

AU - Califano, A.

AU - Cherniack, A. D.

AU - Anastassiou, D.

AU - Bedognetti, D.

AU - Rao, A.

AU - Chen, K.

AU - Krasnitz, A.

AU - Hu, H.

AU - Malta, T. M.

AU - Noushmehr, H.

AU - Pedamallu, C. S.

AU - Bullman, S.

AU - Ojesina, A. I.

AU - Lamb, A.

AU - Zhou, W.

AU - Shen, H.

AU - Choueiri, T. K.

AU - Weinstein, J. N.

AU - Guinney, J.

AU - Saltz, J.

AU - Holt, R. A.

AU - Rabkin, C. E.

AU - Network, Cancer Genome Atlas Research

AU - Lazar, A. J.

AU - Serody, J. S.

AU - Demicco, E. G.

AU - Disis, M. L.

AU - Vincent, B. G.

AU - Shmulevich, L.

AU - Marino, M. (come contributors)

N1 - LR: 20180714; CI: Copyright (c) 2018; GR: U24 CA143882/CA/NCI NIH HHS/United States; GR: U54 CA209997/CA/NCI NIH HHS/United States; GR: U54 HG003067/HG/NHGRI NIH HHS/United States; GR: U24 CA143835/CA/NCI NIH HHS/United States; GR: U24 CA180924/CA/NCI NIH HHS/United States; GR: U24 CA143866/CA/NCI NIH HHS/United States; GR: U24 CA210950/CA/NCI NIH HHS/United States; GR: U24 CA143845/CA/NCI NIH HHS/United States; GR: U24 CA143799/CA/NCI NIH HHS/United States; GR: U54 HG003273/HG/NHGRI NIH HHS/United States; GR: U24 CA144025/CA/NCI NIH HHS/United States; GR: S10 OD012351/OD/NIH HHS/United States; GR: U24 CA143840/CA/NCI NIH HHS/United States; GR: U24 CA143843/CA/NCI NIH HHS/United States; GR: U24 CA143858/CA/NCI NIH HHS/United States; GR: U24 CA143848/CA/NCI NIH HHS/United States; GR: U24 CA210957/CA/NCI NIH HHS/United States; GR: U54 HG003079/HG/NHGRI NIH HHS/United States; GR: U24 CA210949/CA/NCI NIH HHS/United States; GR: U24 CA143883/CA/NCI NIH HHS/United States; GR: S10 OD021764/OD/NIH HHS/United States; GR: U24 CA143867/CA/NCI NIH HHS/United States; GR: R35 CA197745/CA/NCI NIH HHS/United States; GR: R50 CA221675/CA/NCI NIH HHS/United States; GR: U24 CA210990/CA/NCI NIH HHS/United States; JID: 9432918; NIHMS958212; OTO: NOTNLM; PMCR: 2019/04/17 00:00; 2017/07/21 00:00 [received]; 2018/01/23 00:00 [revised]; 2018/03/21 00:00 [accepted]; 2019/04/17 00:00 [pmc-release]; 2018/04/10 06:00 [pubmed]; 2018/04/10 06:00 [medline]; 2018/04/10 06:00 [entrez]; ppublish

PY - 2018/4/17

Y1 - 2018/4/17

N2 - 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-gamma dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-beta 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.

AB - 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-gamma dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-beta 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.

KW - cancer genomics

KW - immune subtypes

KW - immuno-oncology

KW - immunomodulatory

KW - immunotherapy

KW - integrative network analysis

KW - tumor immunology

KW - tumor microenvironment

U2 - S1074-7613(18)30121-3 [pii]

DO - S1074-7613(18)30121-3 [pii]

M3 - Article

VL - 48

SP - 812-830.e14

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 4

ER -