HYDROGEN PEROXIDE IMPEDES NK CELL AND T CELL MEDIATED CYTOTOXICITY AGAINST COLON CANCER CELL

Abstract

Although hydrogen peroxide (H2O2) is an admirable treatment for many cancer types, but the clinical impact of H2O2 on immune cells is not known. In the present study, we have demonstrated that H2O2 is a crucial factor to determine the cell mediated cytotoxicity of immune cells to the cancer cells. Natural killer (NK) cells and T cells were isolated from healthy donors and were activated and enriched the population at ex-vivo condition. At day14, activated NK and T cells were exposed to colon cancer cell at the ratio of 10:1 (Effector: Target) with or without H2O2 (50 µM and 100µM) treatment for 6 h and 12 h. Cytotoxicity assay showed that cytotolytic ability of NK and T cells was strongly suppressed in the presence of H2O2. H2O2 induced NK and T cell dysfunction was analyzed and results demonstrated that NK and T cells were lose their viability on dose and time dependent manner. Also, flow cytometry analysis revealed that H2O2 significantly suppresses the activation and proliferation CD8 T cell population. Whereas, NK cell subset (CD56bright and CD56dim) was dramatically altered by H2O2. When exposed to H2O2, CD56dim population was considerably increased at different time points.  Hence, we conclude that H2O2 directly or functionally defect the NK and T cell mediated cytotoxicity and however, further studies are warranted to confirm the concept with mild dose of H2O2 with different cancer cell lines.