Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

Restricting tumor lactic acid metabolism using dichloroacetate improves T cell functions

Thu Oct 6 07:11:23 2022

(2022) Restricting tumor lactic acid metabolism using dichloroacetate improves T cell functions. Bmc Cancer. p. 12.

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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 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.

Item Type: Article
Creators:
CreatorsEmail
Rostamian, H.UNSPECIFIED
Khakpoor-Koosheh, M.UNSPECIFIED
Jafarzadeh, L.UNSPECIFIED
Masoumi, E.UNSPECIFIED
Fallah-Mehrjardi, K.UNSPECIFIED
Tavassolifar, M. J.UNSPECIFIED
Pawelek, J. M.UNSPECIFIED
Mirzaei, H. R.UNSPECIFIED
Hadjati, J.UNSPECIFIED
Keywords: Metabolism Lactic acid Cancer T cell Dichloroacetate Immunotherapy high lactate levels immune resistance redox regulation cancer Oncology
Divisions:
Page Range: p. 12
Journal or Publication Title: Bmc Cancer
Journal Index: ISI
Volume: 22
Number: 1
Identification Number: https://doi.org/10.1186/s12885-021-09151-2
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/3842

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