Roza Nurieva
MD Anderson Cancer Center, TX, USA
Title: Absence of Grail promotes CD8+ T cell anti-tumor activity
Biography
Biography: Roza Nurieva
Abstract
T cell tolerance is a major obstacle to successful cancer immunotherapy; thus, it is of high priority to develop strategies to break immune tolerance. Here we report that expression of the E3 ubiquitin ligase Grail is significantly upregulated in CD8+ T cells infiltrated into transplanted lymphoma tumors and Grail-deficiency confers long-term tumor control. Importantly, therapeutic transfer of Grail-deficient CD8+ T cells was sufficient to repress established tumors. Mechanistically, loss of Grail enhanced anti-tumor reactivity and functionality of CD8+ T cells. In addition, Grail deficient CD8+ T cells exhibited increased IL-21R expression and hyper-responsiveness to IL-21 signaling as Grail promotes IL-21R ubiquitination and degradation. Moreover, CD8+ T cells isolated from lymphoma patients expressed high levels of Grail and lower levels of IL-21R compared with normal donors. Altogether, our data demonstrates that Grail is a crucial factor controlling CD8+ T cell function and is a potential target to improve CTL activity.