Genomic analysis of immune cell infiltrates across 11 tumor types

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Abstract

Background: Immune infiltration of the tumor microenvironment has been associated with improved survival for some patients with solid tumors. The precise makeup and prognostic relevance of immune infiltrates across a broad spectrum of tumors remain unclear. Methods: Using mRNA sequencing data from The Cancer Genome Atlas (TCGA) from 11 tumor types representing 3485 tumors, we evaluated lymphocyte and macrophage gene expression by tissue type and by genomic subtypes defined within and across tumor tissue of origin (Cox proportional hazards, Pearson correlation). We investigated clonal diversity of B-cell infiltrates through calculating B-cell receptor (BCR) repertoire sequence diversity. All statistical tests were two-sided. Results: High expression of T-cell and B-cell signatures predicted improved overall survival across many tumor types including breast, lung, and melanoma (breast CD8-T-Cells hazard ratio [HR] = 0.36, 95% confidence interval [CI] = 0.16 to 0.81, P = .01; lung adenocarcinoma B-Cell-60gene HR=0.71, 95% CI=0.58 to 0.87, P = 7.80E-04; melanoma LCK HR=0.86, 95% CI=0.79 to 0.94, P = 6.75E-04). Macrophage signatures predicted worse survival in GBM, as did B-cell signatures in renal tumors (Glioblastoma Multiforme [GBM]: macrophages HR=1.62, 95% CI=1.17 to 2.26, P = .004; renal: B-Cell-60gene HR=1.17, 95% CI=1.04 to 1.32, P = .009). BCR diversity was associated with survival beyond gene segment expression in melanoma (HR=2.67, 95% CI=1.32 to 5.40, P = .02) and renal cell carcinoma (HR=0.36, 95% CI=0.15 to 0.87, P = .006). Conclusions: These data support existing studies suggesting that in diverse tissue types, heterogeneous immune infiltrates are present and typically portend an improved prognosis. In some tumor types, BCR diversity was also associated with survival. Quantitative genomic signatures of immune cells warrant further testing as prognostic markers and potential biomarkers of response to cancer immunotherapy.

LanguageEnglish (US)
Article numberdjw144
JournalJournal of the National Cancer Institute
Volume108
Issue number11
DOIs
StatePublished - Jan 1 2016

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B-Lymphocytes
Confidence Intervals
Neoplasms
Melanoma
Survival
Macrophages
Glioblastoma
T-Lymphocytes
Kidney
Gene Expression
Tumor Microenvironment
Atlases
Renal Cell Carcinoma
Immunotherapy
Breast
Biomarkers
Genome
Lymphocytes
Breast Neoplasms
Lung

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{eab544b2c03542058f8798ca47413d08,
title = "Genomic analysis of immune cell infiltrates across 11 tumor types",
abstract = "Background: Immune infiltration of the tumor microenvironment has been associated with improved survival for some patients with solid tumors. The precise makeup and prognostic relevance of immune infiltrates across a broad spectrum of tumors remain unclear. Methods: Using mRNA sequencing data from The Cancer Genome Atlas (TCGA) from 11 tumor types representing 3485 tumors, we evaluated lymphocyte and macrophage gene expression by tissue type and by genomic subtypes defined within and across tumor tissue of origin (Cox proportional hazards, Pearson correlation). We investigated clonal diversity of B-cell infiltrates through calculating B-cell receptor (BCR) repertoire sequence diversity. All statistical tests were two-sided. Results: High expression of T-cell and B-cell signatures predicted improved overall survival across many tumor types including breast, lung, and melanoma (breast CD8-T-Cells hazard ratio [HR] = 0.36, 95{\%} confidence interval [CI] = 0.16 to 0.81, P = .01; lung adenocarcinoma B-Cell-60gene HR=0.71, 95{\%} CI=0.58 to 0.87, P = 7.80E-04; melanoma LCK HR=0.86, 95{\%} CI=0.79 to 0.94, P = 6.75E-04). Macrophage signatures predicted worse survival in GBM, as did B-cell signatures in renal tumors (Glioblastoma Multiforme [GBM]: macrophages HR=1.62, 95{\%} CI=1.17 to 2.26, P = .004; renal: B-Cell-60gene HR=1.17, 95{\%} CI=1.04 to 1.32, P = .009). BCR diversity was associated with survival beyond gene segment expression in melanoma (HR=2.67, 95{\%} CI=1.32 to 5.40, P = .02) and renal cell carcinoma (HR=0.36, 95{\%} CI=0.15 to 0.87, P = .006). Conclusions: These data support existing studies suggesting that in diverse tissue types, heterogeneous immune infiltrates are present and typically portend an improved prognosis. In some tumor types, BCR diversity was also associated with survival. Quantitative genomic signatures of immune cells warrant further testing as prognostic markers and potential biomarkers of response to cancer immunotherapy.",
author = "Iglesia, {Michael D.} and Parker, {Joel S.} and Hoadley, {Katherine A.} and Serody, {Jonathan S.} and Perou, {Charles M.} and Vincent, {Benjamin G.}",
year = "2016",
month = "1",
day = "1",
doi = "10.1093/jnci/djw144",
language = "English (US)",
volume = "108",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "11",

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T1 - Genomic analysis of immune cell infiltrates across 11 tumor types

AU - Iglesia,Michael D.

AU - Parker,Joel S.

AU - Hoadley,Katherine A.

AU - Serody,Jonathan S.

AU - Perou,Charles M.

AU - Vincent,Benjamin G.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Immune infiltration of the tumor microenvironment has been associated with improved survival for some patients with solid tumors. The precise makeup and prognostic relevance of immune infiltrates across a broad spectrum of tumors remain unclear. Methods: Using mRNA sequencing data from The Cancer Genome Atlas (TCGA) from 11 tumor types representing 3485 tumors, we evaluated lymphocyte and macrophage gene expression by tissue type and by genomic subtypes defined within and across tumor tissue of origin (Cox proportional hazards, Pearson correlation). We investigated clonal diversity of B-cell infiltrates through calculating B-cell receptor (BCR) repertoire sequence diversity. All statistical tests were two-sided. Results: High expression of T-cell and B-cell signatures predicted improved overall survival across many tumor types including breast, lung, and melanoma (breast CD8-T-Cells hazard ratio [HR] = 0.36, 95% confidence interval [CI] = 0.16 to 0.81, P = .01; lung adenocarcinoma B-Cell-60gene HR=0.71, 95% CI=0.58 to 0.87, P = 7.80E-04; melanoma LCK HR=0.86, 95% CI=0.79 to 0.94, P = 6.75E-04). Macrophage signatures predicted worse survival in GBM, as did B-cell signatures in renal tumors (Glioblastoma Multiforme [GBM]: macrophages HR=1.62, 95% CI=1.17 to 2.26, P = .004; renal: B-Cell-60gene HR=1.17, 95% CI=1.04 to 1.32, P = .009). BCR diversity was associated with survival beyond gene segment expression in melanoma (HR=2.67, 95% CI=1.32 to 5.40, P = .02) and renal cell carcinoma (HR=0.36, 95% CI=0.15 to 0.87, P = .006). Conclusions: These data support existing studies suggesting that in diverse tissue types, heterogeneous immune infiltrates are present and typically portend an improved prognosis. In some tumor types, BCR diversity was also associated with survival. Quantitative genomic signatures of immune cells warrant further testing as prognostic markers and potential biomarkers of response to cancer immunotherapy.

AB - Background: Immune infiltration of the tumor microenvironment has been associated with improved survival for some patients with solid tumors. The precise makeup and prognostic relevance of immune infiltrates across a broad spectrum of tumors remain unclear. Methods: Using mRNA sequencing data from The Cancer Genome Atlas (TCGA) from 11 tumor types representing 3485 tumors, we evaluated lymphocyte and macrophage gene expression by tissue type and by genomic subtypes defined within and across tumor tissue of origin (Cox proportional hazards, Pearson correlation). We investigated clonal diversity of B-cell infiltrates through calculating B-cell receptor (BCR) repertoire sequence diversity. All statistical tests were two-sided. Results: High expression of T-cell and B-cell signatures predicted improved overall survival across many tumor types including breast, lung, and melanoma (breast CD8-T-Cells hazard ratio [HR] = 0.36, 95% confidence interval [CI] = 0.16 to 0.81, P = .01; lung adenocarcinoma B-Cell-60gene HR=0.71, 95% CI=0.58 to 0.87, P = 7.80E-04; melanoma LCK HR=0.86, 95% CI=0.79 to 0.94, P = 6.75E-04). Macrophage signatures predicted worse survival in GBM, as did B-cell signatures in renal tumors (Glioblastoma Multiforme [GBM]: macrophages HR=1.62, 95% CI=1.17 to 2.26, P = .004; renal: B-Cell-60gene HR=1.17, 95% CI=1.04 to 1.32, P = .009). BCR diversity was associated with survival beyond gene segment expression in melanoma (HR=2.67, 95% CI=1.32 to 5.40, P = .02) and renal cell carcinoma (HR=0.36, 95% CI=0.15 to 0.87, P = .006). Conclusions: These data support existing studies suggesting that in diverse tissue types, heterogeneous immune infiltrates are present and typically portend an improved prognosis. In some tumor types, BCR diversity was also associated with survival. Quantitative genomic signatures of immune cells warrant further testing as prognostic markers and potential biomarkers of response to cancer immunotherapy.

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