Absence of Grail promotes CD8⁺ T cell anti-tumour activity.

ABSTRACT: T-cell tolerance is a major obstacle to successful cancer immunotherapy; thus, developing strategies to break immune tolerance is a high priority. Here we show that expression of the E3 ubiquitin ligase Grail is upregulated in CD8⁺ T cells that have infiltrated into transplanted lymphoma tumours, and Grail deficiency confers long-term tumour control. Importantly, therapeutic transfer of Grail-deficient CD8⁺ T cells is sufficient to repress established tumours. Mechanistically, loss of Grail enhances anti-tumour reactivity and functionality of CD8⁺ T cells. In addition, Grail-deficient CD8⁺ T cells have increased IL-21 receptor (IL-21R) expression and hyperresponsiveness to IL-21 signalling as Grail promotes IL-21R ubiquitination and degradation.

SUBMITTER: Haymaker C 

PROVIDER: S-EPMC5552797 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature