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Cancer SLC6A6-mediated taurine uptake impairs CD8+ T cell antitumor immunity by upregulating immune checkpoints [mouse RNA-Seq]

ABSTRACT: Taurine is a supplement used to bolster immunity, but how taurine affects antitumor immunity remains largely unknown. We report that SLC6A6-mediated uptake of taurine by gastric cancer (GC) cells results in T cell exhaustion and cancer progression. SLC6A6 was correlated with GC aggressiveness and poor outcomes, and taurine uptake increased GC proliferation, survival, and cell motility. Taurine significantly increased CD8+ T cell infiltration and cytotoxic effector expression in GC tumors. Mechanistically, taurine deprivation in CD8+ T cells increased ER stress and the unfolded protein response, resulting in AT4 transcription, which acts as a switch for T cell exhaustion. SLC6A6 was transactivated by SP1 in GC cells, with a strong correlation between SP1 and SLC6A6 in GC patients. The SP1-SLC6A6 axis was triggered by chemotherapy. Our findings reveal that SLC6A6-mediated taurine consumption impacts immune evasion and propose that taurine supplementation might reinvigorate CD8+ T cell response and enhance therapy efficacy.

ORGANISM(S): Mus musculus

PROVIDER: GSE249288 | GEO | 2024/04/01

REPOSITORIES: GEO

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Cancer SLC6A6-mediated taurine uptake impairs CD8+ T cell antitumor immunity by upregulating immune checkpoints [mouse RNA-Seq]

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