IRE1α-XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity.

ABSTRACT: Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function^1-4. However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals. Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies^5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response^9,10 in T cells to control their mitochondrial respiration and anti-tumour function. In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression. Malignant as

SUBMITTER: Song M 

PROVIDER: S-EPMC6237282 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature