Lactic acid produced by tumors has been shown to overcome immune surveillance, by suppressing the activation and function of T cells in the tumor microenvironment. The strategies employed to impair tumor cell glycolysis could improve immunosurveillance and tumor growth regulation. Dichloroacetate (DCA) limits the tumorderived lactic acid by altering the cancer cell metabolism. | Rostamian et al. BMC Cancer 2022 22 39 https s12885-021-09151-2 RESEARCH Open Access Restricting tumor lactic acid metabolism using dichloroacetate improves T cell functions Hosein Rostamian1 Mohammad Khakpoor Koosheh1 Leila Jafarzadeh1 2 Elham Masoumi3 Keyvan Fallah Mehrjardi1 Mohammad Javad Tavassolifar1 John M. Pawelek4 Hamid Reza Mirzaei1 and Jamshid Hadjati1 Abstract Background Lactic acid produced by tumors has been shown to overcome immune surveillance by suppressing the activation and function of T cells in the tumor microenvironment. The strategies employed to impair tumor cell glycolysis could improve immunosurveillance and tumor growth regulation. Dichloroacetate DCA limits the tumor- derived lactic acid by altering the cancer cell metabolism. In this study the effects of lactic acid on the activation and function of T cells were analyzed by assessing T cell prolif eration cytokine production and the cellular redox state of T cells. We examined the redox system in T cells by analyz ing the intracellular level of reactive oxygen species ROS superoxide and glutathione and gene expression of some proteins that have a role in the redox system. Then we co-cultured DCA-treated tumor cells with T cells to examine the effect of reduced tumor-derived lactic acid on proliferative response cytokine secretion and viability of T cells. Result We found that lactic acid could dampen T cell function through suppression of T cell proliferation and cytokine production as well as restrain the redox system of T cells by decreasing the production of oxidant and antioxidant molecules. DCA decreased the concentration of tumor lactic acid by manipulating glucose metabolism in tumor cells. This led to increases in T cell proliferation and cytokine production and also rescued the T cells from apoptosis. Conclusion Taken together our results suggest accumulation of lactic acid in the tumor microenvironment restricts T cell responses and could prevent the success .
