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 (CD56^bright and CD56^dim) was dramatically altered by H₂O₂. When exposed to H₂O₂, CD56^dim 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.