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ATF4-SLC7A11-GSH axis mediates the acquisition of immunosuppressive properties by activated CD4+ T cells in low arginine condition

ABSTRACT: The tumor microenvironment (TME) is restricted in metabolic nutrients including the semi-essential amino acid arginine. While complete arginine deprivation causes T cell dysfunction, it remains unclear how arginine levels fluctuate in the TME to shape T cell fates. Here, we found that the 20μM low arginine condition, as present in multiple TMEs, confers upon activated T cells Treg-like immunosuppressive capacities. In vivo mouse tumor models and human scRNA-Seq datasets reveal positive correlations between low arginine condition and intratumoral Treg accumulation. Mechanistically, low-arginine activated T cells engage in metabolic and transcriptional reprogramming, using the ATF4-SLC7A11-GSH axis, to preserve their suppressive function. These findings improve our understanding of the role of arginine in human T cell biology with potential applications for immunotherapy strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE256171 | GEO | 2024/02/25

REPOSITORIES: GEO

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ATF4-SLC7A11-GSH axis mediates the acquisition of immunosuppressive properties by activated CD4+ T cells in low arginine condition

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