CD39 Tumor Infiltrating T Cells from Colorectal Cancers Exhibit Dysfunctional Phenotype

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2024 Mar 8

PMID 38455401

Authors

Yuan Feng

Xin Xu

Jiaxin Zhang

Christopher Sanderson

Jun Xia

Zhang Bu

Yili Yang

Peng Yang

Zhiliang Lu

Affiliations

Soon will be listed here.

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.

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