Human recombinant soluble PD1 can interference in T cells and Treg cells function in response to MDA-MB-231 cancer cell line.

Abstract

Objectives: PD1/PDL1 pathway targeting using antibodies shows immune related adverse events in patients with tumors. The masking of PD1 ligand by soluble human PD-1 (shPD-1) probably inhibits the PD1/PDL1 interaction between T cells and tumor cells. Accordingly, the goal of this study was to produce human recombinant PD-1-secreting cells and find out how soluble human PD-1 affects T lymphocyte function.

Methods: An inducible construct of the human PD-1 secreting gene under hypoxia condition was synthesized. The construct was transfected into the MDA-MB-231 cell line. In six groups exhausted T lymphocytes were co-cultured with transfected or non-transfected MDA-MB-231 cell lines. The effect of shPD-1 on IFNγ production, Treg cell's function, CD107a expression, apoptosis, and proliferation was assessed by ELISA and flow cytometry, respectively.

Results: The results of this study showed that shPD-1 inhibits PD-1/PD-L1 interaction and enhances T lymphocyte responses through a significant increase in IFNγ production and CD107a expression. In addition, in the presence of shPD-1, the percentage of Treg cells decreased, while MDA-MB-231 cell apoptosis increased.

Conclusions: We concluded that the human PD-1 secreting construct induced under hypoxia condition inhibits the interaction of PD-1/PD-L1 and enhances T lymphocyte responses in tumor environments and chronic infections.