Expression Profiles of TN Breast Tumors (Stromal, Epithelial)

Description: Engaging the immune system promises to be key for optimal cancer therapy, especially in hard-to-treat disease such as triple-negative breast cancer (TNBC). However, the immune microenvironment remains poorly understood. Using gene expression based on laser capture microdissection, we identify three distinct tumor microenvironments associated with CD8+ T cell localization patterns and outcome in TNBC. An immunoreactive microenvironment is defined by granzyme B-positive CD8+ T cell infiltration, a type I interferon signature, tumor expression of PD-L1 and good outcome. In contrast, tumors with an immune-cold microenvironment display restriction of CD8+ T cells to tumor margins, elevated tumor expression of the immunosuppressive marker B7-H4, a signature of desmoplastic stroma and poor outcome. A third distinct immunomodulatory microenvironment associated with poor outcome is enriched for IL-17-producing cells and neutrophils, as well as stroma-restricted localisation of CD8+ T cells. These distinct immune microenvironments have implications for TNBC patient stratification for current and future therapies.