The prognostic value of CD39+CD8+ T cells as a potential surrogate marker of tumor-specific T cells in Asian triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that is generally associated with poor prognosis in affected patients. Unfortunately, recently approved immune checkpoint inhibitors are efficacious in only a subset of patients. A surrogate marker for tumor-specific CD8+ T cells is urgently required to clarify the mechanisms of antitumor immune responses and help prognosticate TNBC patients. Here, we conducted a comparative interrogation of TNBC to evaluate the potential of CD39 as a surrogate marker of tumor-specific T cells. We first used flow cytometry to study more than 12,000 tumor-specific CD8+ T cells within both peripheral blood mononuclear cells and tumor-infiltrating lymphocyte populations in a mouse TNBC model and found that more than 99% of tumor-specific CD8+ T cells were present in the CD39+ subset. Multiplex immunohistochemistry/immunofluorescence staining demonstrated that the proportion of CD39+CD8+ T cells in human TNBC tumors correlated with improved overall survival. The frequencies of other CD39+ immune infiltrates, such as CD39+CD68+ macrophages, also correlated with improved OS. Thus CD39+CD8+ T cells might help predict prognosis in patients with TNBC.