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Absence of Grail promotes CD8+ T cell anti-tumour activity.
- Source :
- Nature Communications; 8/10/2017, Vol. 8 Issue 1, p1-14, 14p
- Publication Year :
- 2017
-
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<superscript>+</superscript> T cells that have infiltrated into transplanted lymphoma tumours, and Grail deficiency confers long-term tumour control. Importantly, therapeutic transfer of Grail-deficient CD8<superscript>+</superscript> T cells is sufficient to repress established tumours. Mechanistically, loss of Grail enhances anti-tumour reactivity and functionality of CD8<superscript>+</superscript> T cells. In addition, Grail-deficient CD8<superscript>+</superscript> T cells have increased IL-21 receptor (IL-21R) expression and hyperresponsiveness to IL-21 signalling as Grail promotes IL-21R ubiquitination and degradation. Moreover, CD8<superscript>+</superscript> T cells isolated from lymphoma patients express higher levels of Grail and lower levels of IL-21R, compared with CD8<superscript>+</superscript> T cells from normal donors. Our data demonstrate that Grail is a crucial factor controlling CD8<superscript>+</superscript> T-cell function and is a potential target to improve cytotoxic T-cell activity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 8
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 138013441
- Full Text :
- https://doi.org/10.1038/s41467-017-00252-w