| Autor: |
Haymaker, Cara, Yi Yang, Junmei Wang, Qiang Zou, Sahoo, Anupama, Alekseev, Andrei, Singh, Divyendu, Ritthipichai, Krit, Hailemichael, Yared, Hoang, Oanh N., Hong Qin, Schluns, Kimberly S., Tiejun Wang, Overwijk, Willem W., Shao-Cong Sun, Bernatchez, Chantale, Kwak, Larry W., Neelapu, Sattva S., Nurieva, Roza |
| Předmět: |
|
| Zdroj: |
Nature Communications; 8/10/2017, Vol. 8 Issue 1, p1-14, 14p |
| Abstrakt: |
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. Moreover, CD8+ T cells isolated from lymphoma patients express higher levels of Grail and lower levels of IL-21R, compared with CD8+ T cells from normal donors. Our data demonstrate that Grail is a crucial factor controlling CD8+ T-cell function and is a potential target to improve cytotoxic T-cell activity. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
