The Role And Mechanism Of γδT Cells In Adoptive Cellular Immunotherapy For Colon Cance

Background:Vγ9Vδ2γδT (Vδ2T) cells-based adoptive immunotherapy for most solid tumors has limited success. This study aims to determine whether Vδ1γδT (Vδ1T) cells can be used as an effective adoptive cellular immunotherapy for solid tumors such as colon cancer.Methods:The characteristics and cytotoxicity against human colon cancer between freshly isolated Vδ1and V82T cells were evaluated. To efficiently expand Vδ1T cells, we stimulated yST cells with phytohemagglutinin (PHA) and interleukin-7(IL-7) combination for14days. The anti-cancer activity of expanded Vδ1and VS2T cells was assessed in vitro and in a xenografted human colon cancer mouse model. To investigate the underlying killing mechanism employed by Vδ1T cells, we performed cytotoxicity assay in a transwell co-culture system and antibody blocking experiment.Results:Freshly isolated Vδ1T cells from human peripheral blood (PB) exhibit more potent cytotoxicity against adherent and sphere-forming colon cancer cells than Vδ2T cells in vitro. Upon stimulation with PHA and IL-7, Vδ1T cells from PB of both healthy donors and colon cancer patientswere preferentially expanded and highly expressed cytotoxicity-related molecules, chemokine receptors and cytokines with enhanced cytotoxicity against adherent and sphere-forming colon cancer cells in a cell-contact dependent manner. In addition, ex vivo expanded V81T cells by PHA and IL-7showed proliferation and survival advantage partly through an IL-2signaling pathway. Furthermore, PHA and IL-7expanded V81T cells restrained the tumor growth and prolonged the tumor-burdened survival of human colon carcinoma xenografted mice.Conclusion:Our findings suggest that human PB V81T cells expanded by PHA and IL-7are a promising candidate for anticancer adoptive immunotherapy for human solid tumors such as colon cancer.