期刊
BMC CANCER
卷 22, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12885-021-09151-2
关键词
Metabolism; Lactic acid; Cancer; T cell; Dichloroacetate; Immunotherapy
类别
资金
- Tehran University of medical sciences [42010]
Lactic acid produced by tumors can suppress the activation and function of T cells in the tumor microenvironment, while Dichloroacetate (DCA) can limit the tumor-derived lactic acid and improve T cell proliferation and cytokine production. Accumulation of lactic acid in the tumor microenvironment restricts T cell responses and DCA supports anti-tumor responses of T cells by metabolic reprogramming of tumor cells.
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 proliferation, cytokine production and the cellular redox state of T cells. We examined the redox system in T cells by analyzing 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 of T cell therapy. DCA supports anti-tumor responses of T cells by metabolic reprogramming of tumor cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据