CTLA-4 blockade drives loss of T_reg stability in glycolysis-low tumours.

ABSTRACT: Limiting metabolic competition in the tumour microenvironment may increase the effectiveness of immunotherapy. Owing to its crucial role in the glucose metabolism of activated T cells, CD28 signalling has been proposed as a metabolic biosensor of T cells¹. By contrast, the engagement of CTLA-4 has been shown to downregulate T cell glycolysis¹. Here we investigate the effect of CTLA-4 blockade on the metabolic fitness of intra-tumour T cells in relation to the glycolytic capacity of tumour cells. We found that CTLA-4 blockade promotes metabolic fitness and the infiltration of immune cells, especially in glycolysis-low tumours. Accordingly, treatment with anti-CTLA-4 antibodies improved the therapeutic outcomes of mice bearing glycolysis-defective tumours. Notably, tumo

SUBMITTER: Zappasodi R 

PROVIDER: S-EPMC8057670 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature