The Prognostic Value of CD39 as a Marker of Tumor-Specific T Cells in Triple-Negative Breast Cancer in Asian Women

Abstract

Triple-negative breast cancer (TNBC) has a poor prognosis with limited therapeutic options available for affected patients. Efforts are ongoing to identify surrogate markers for tumor-specific CD8⁺ T cells that can predict the response to immune checkpoint inhibitor (ICI) therapies, such as programmed cell death protein 1 or programmed cell death ligand-1 blockade. We have previously identified tumor-specific CD39⁺CD8⁺ T cells in non-small cell lung cancer that might help predict patient responses to programmed cell death protein 1 or programmed cell death ligand-1 blockade. Based on this finding, we conducted a comparative interrogation of TNBC in an Asian cohort to evaluate the potential of CD39 as a surrogate marker of tumor-specific CD8⁺ T cells. Using ICI-treated TNBC mouse models (n = 24), flow cytometric analyses of peripheral blood mononuclear cells and tumor-infiltrating lymphocytes revealed that >99% of tumor-specific CD8⁺ T cells also expressed CD39. To investigate the relationship between CD39⁺CD8⁺ T-cell density and CD39 expression with disease prognosis, we performed multiplex immunohistochemistry staining on treatment-naive human TNBC tissues (n = 315). We saw that the proportion of CD39⁺CD8⁺ T cells in human TNBC tumors correlated with improved overall survival, as did the densities of other CD39⁺ immune cell infiltrates, such as CD39⁺CD68⁺ macrophages. Finally, increased CD39 expression on CD8⁺ T cells was also found to predict the response to ICI therapy (pembrolizumab) in a separate cohort of 11 TNBC patients. These findings support the potential of CD39⁺CD8⁺ T-cell density as a prognostic factor in Asian TNBC patients.

Keywords: Asian TNBC; CD39(+)CD8(+) T cells; ICI response; TNBC prognosis; tumor-specific CD8(+) T cells.