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 journalArticle

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 languageEnglish
Pages (from-to)812-830.e14
JournalImmunity
Volume48
Issue number4
DOIs
Publication statusPublished - Apr 17 2018
Externally publishedYes

Fingerprint

Neoplasms
Genetic Epigenesis
Lymphocytes
Th2 Cells
Th1 Cells
Aneuploidy
MicroRNAs
Cell Communication
Transforming Growth Factor beta
Wound Healing
Leukocytes
Macrophages
Cell Proliferation
Gene Expression
Mutation

Keywords

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

Cite this

Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Yang, T. H. O., ... 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 journalArticle

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 DL, Brown SD, Wolf D, Bortone DS, Yang THO et al. The Immune Landscape of Cancer. Immunity. 2018 Apr 17;48(4):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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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 -