CD39+ tumor infiltrating T cells from colorectal cancers exhibit dysfunctional phenotype

Abstract

Recent studies revealed that CD39 was highly expressed in tumor-specific CD4⁺ tumor infiltrating lymphocytes (TILs). However, the divergent function of CD39⁺ T cells remains to be elucidated in colorectal cancer (CRC). In this study, T cells from CRC patients and tumor-bearing mice were isolated to evaluate the function of CD39 in T cells. We found that CD39 was elevated in intratumoral T cells from CRC patients, and negatively correlated with cytokine secretion capacity. T cell activation induced CD39 expression, and CD39⁺ T cells produced more IFN-γ in response to CRC tumor antigens. In addition, CD39⁺ T cells in the spleens of tumor-bearing mice exhibited a stronger anti-tumor activity in vitro than CD39^- T cells, but there was no significant difference in the anti-tumor activities between CD39^- TILs and CD39⁺ TILs. Moreover, we found that CD39⁺ T cells expressed higher checkpoint molecules and contained a higher proportion of Treg cells than CD39^- T cells, suggesting that CD39⁺ T cells may be correlated with an immunosuppressive phenotype. And CD39 expression on T cells could convert pro-inflammatory eATP to immunosuppressive eADO. However, both T cells from the vaccinated-wild-type mice and CD39^-/- mice could recognize and eliminate tumor cells in vitro, and adoptive transfer of these T cells resulted in tumor growth inhibition in tumor-bearing mice. In conclusion, our study revealed the divergent functions of CD39⁺ T cells, which were reactive to tumor antigen but exhibited a dysfunctional phenotype.