Effects of Soluble Human Program Cell Death protein-۱ and Tumor Cells Lysate on Cytotoxicity of CD۸-T Cells

Introduction: CD۸-Th۱ cells are the effector immune cells which could induce apoptosis of tumor cells via cytotoxicity. Program cell death protein-۱ (PD۱)/ligands (PDLs) pathway as an immune-checkpoints pathway, plays role in CD۸-T cells activities. In this study, we produced a soluble form of PD۱ (shPD۱) form and assessed effect of shPD۱ along with tumor lysate on CD۸-Th۱ cell cytotoxicity. Methods: Exhausted T cells were prepared by canavalin-A stimulation and co-cultured with produced shPD۱ and tumor cells lysate for ۶ hours. Tumor cell lysate (MDA-MB-۲۳۱ cells) were prepared by freezing and thawing of tumor cell in -۸۰ᵒC and ۳۷ᵒC. Cytotoxicity of CD۸-T cells were evaluated by flowcytometry. Results: CD۱۰۷a expressions were significantly elevated on T cells (۳۳%±۱.۷) and CD۸-T cells (۴۱%±۲) in co-cultured groups. shPD۱ as a co-stimulatory signal could increase CD۸- T cells cytotoxicity and therefore apoptosis of PD-Ls+ tumor cells through blockade of PD۱/PDLs pathway. In addition, tumor cell line lysate as the source of tumor derived proteins can activate T cells via stimulation of Toll like receptors. Conclusion: shPD۱ and tumor cell lysate might be a potential candidate for restoring the cytotoxicity of T cells in PDLs+ solid (such as breast and colorectal) tumors and therefore induction of apoptosis.