High expression of T-cell and B-cell signatures in infiltrates in the tumor microenvironment predicted improved overall survival across many tumor types, according to a study reported by Iglesia et al in the Journal of the National Cancer Institute. Benjamin Vincent, MD, of UNC (University of North Carolina) Lineberger Comprehensive Cancer Center, is the corresponding author of the Journal of the National Cancer Institute article.
The study involved use of mRNA sequencing using data from The Cancer Genome Atlas from 11 tumor types representing 3,485 tumors. Lymphocyte and macrophage gene expression were evaluated by tissue type and genomic subtypes defined within and across the tumor tissue of origin. Clonal diversity of B-cell infiltrates was assessed by calculating the sequence diversity of the B-cell receptor (BCR) repertoire.
Associations With Survival
High expression of T-cell and B-cell signatures predicted improved overall survival across many tumor types, including breast (eg, CD8 T cells hazard ratio [HR] = 0.36, 95% confidence interval [CI] = 0.16–0.81, P = .01), head and neck, lung adenocarcinoma (eg, B-cell 60-gene signature HR = 0.71, 95% CI = 0.58–0.87, P < .05), melanoma (eg, T-cell LCK signature HR = 0.86, 95% CI = 0.79–0.94, P < .05), and endometrial cancers. Macrophage signatures were associated with worse survival in glioblastoma multiforme (macrophages HR = 1.62, 95% CI = 0.17–2.26, P = .004), and B-cell signatures were associated with worse survival in renal tumors (B-cell 60-gene signature HR = 1.17, 95% CI = 1.04–1.32, P = .009). BCR diversity was associated with poorer survival in melanoma (HR = 2.67, 95% CI = 1.32–5.40, P = .02) and better survival in renal cell carcinoma (HR = 0.36, 95% CI = 0.15–0.87, P = .006) beyond the associations observed for gene-segment expression.
The investigators concluded: “These data support existing studies suggesting that in diverse tissue types, heterogeneous immune infiltrates are present and typically portend an improved prognosis. Quantitative genomic signatures of immune cells warrant further testing as prognostic markers and potential biomarkers of response to cancer immunotherapy.”
The study was supported by The Cancer Genome Atlas, National Cancer Institute Breast Specialized Programs of Research Excellence program, Breast Cancer Research Foundation, UNC University Cancer Research Fund, UNC Oncology Clinical Translational Research Training Program, and William Guy Forbeck Research Foundation. ■