title: Genomic Analysis of Immune Cell Infiltrates Across 11 Tumor Types.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Affiliations of authors: Lineberger Comprehensive Cancer Center (MDI, JSP, KAH, JSS, CMP, BGV), Curriculum in Genetics and Molecular Biology (MDI, JSP), Department of Medicine (JSS, BGV), Department of Genetics (KAH, CMP), Department of Microbiology and Immunology (JSS), and Department of Pathology & Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, Chapel Hill, NC.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Iglesia
authors.affiliation: Affiliations of authors: Lineberger Comprehensive Cancer Center (MDI, JSP, KAH, JSS, CMP, BGV), Curriculum in Genetics and Molecular Biology (MDI, JSP), Department of Medicine (JSS, BGV), Department of Genetics (KAH, CMP), Department of Microbiology and Immunology (JSS), and Department of Pathology & Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, Chapel Hill, NC.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: Affiliations of authors: Lineberger Comprehensive Cancer Center (MDI, JSP, KAH, JSS, CMP, BGV), Curriculum in Genetics and Molecular Biology (MDI, JSP), Department of Medicine (JSS, BGV), Department of Genetics (KAH, CMP), Department of Microbiology and Immunology (JSS), and Department of Pathology & Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, Chapel Hill, NC.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hoadley
authors.affiliation: Affiliations of authors: Lineberger Comprehensive Cancer Center (MDI, JSP, KAH, JSS, CMP, BGV), Curriculum in Genetics and Molecular Biology (MDI, JSP), Department of Medicine (JSS, BGV), Department of Genetics (KAH, CMP), Department of Microbiology and Immunology (JSS), and Department of Pathology & Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, Chapel Hill, NC.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Serody
authors.affiliation: Affiliations of authors: Lineberger Comprehensive Cancer Center (MDI, JSP, KAH, JSS, CMP, BGV), Curriculum in Genetics and Molecular Biology (MDI, JSP), Department of Medicine (JSS, BGV), Department of Genetics (KAH, CMP), Department of Microbiology and Immunology (JSS), and Department of Pathology & Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, Chapel Hill, NC.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Affiliations of authors: Lineberger Comprehensive Cancer Center (MDI, JSP, KAH, JSS, CMP, BGV), Curriculum in Genetics and Molecular Biology (MDI, JSP), Department of Medicine (JSS, BGV), Department of Genetics (KAH, CMP), Department of Microbiology and Immunology (JSS), and Department of Pathology & Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, Chapel Hill, NC.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Vincent
mesh_terms: D001402:B-Lymphocytes; D015870:Gene Expression; D023281:Genomics; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating; D008264:Macrophages; D009369:Neoplasms / Q000276:immunology*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D011956:Receptors, Cell Surface / Q000235:genetics*; D015996:Survival Rate; D013601:T-Lymphocytes; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D012333:RNA, Messenger; D011956:Receptors, Cell Surface