Post-transcriptional control of metabolic programs that improve T cell responses against tumors (C02)

事实证明，免疫细胞疗法在治疗某些癌症和部分患者方面非常成功。然而，仍有改进的空间，例如在T细胞对肿瘤的反应中操纵T细胞的代谢程序。RNA结合蛋白Roquin和Regnase-1已被证明控制T细胞生物学和代谢的许多方面，并通过副半胱氨酸酶MALT1的切割以TCR强度依赖的方式失活。在这项提案中，将揭示Roquin和Regnase-1介导的基因调控对CD8+T细胞抗肿瘤反应的贡献，并评估如何将该系统用于免疫细胞治疗。

Immune cell therapies have proven very successful in the treatment of some cancers and in a subset of patients. Nevertheless, there is room for improvement for example by manipulating the metabolic programs of T cells in their responses against tumors. The RNA-binding proteins Roquin and Regnase-1 have been shown to control many aspects of T cell biology and metabolism, and they are inactivated in a TCR-strength dependent manner through cleavage by the paracaspase MALT1. In this proposal will unravel the contributions of Roquin- and Regnase-1-mediated gene regulation to anti-tumor responses of CD8+ T cells and evaluate how to use the system in immune cell therapies.