WEE1 inhibition and tumor immunity

项目摘要 肿瘤采用许多机制来促进免疫逃逸，包括免疫逃逸。 肿瘤微环境中不同免疫抑制细胞的浸润， 调节性T细胞（Treg）。然而，肿瘤细胞内调节肿瘤生长的特定信号 引起肿瘤诱导免疫抑制的TGFAP的募集仍然存在， 难以捉摸根据我们新的初步数据，我们假设WEE1，一个重要的 调节细胞周期检查点，维持免疫抑制和亲， 致瘤微环境，并抑制WEE 1活性，包括通过临床 相关的WEE 1抑制剂，可能是治疗上有益的，通过加强免疫介导的 肿瘤清除率该提案旨在描述新的监管视角 WEE1介导的肿瘤细胞和宿主免疫细胞之间的串扰， 大力推进领域。具体来说，这个项目正在寻找 WEE1介导的Treg调节机制和新的有效的 组合策略因此，我们的工作将确定WEE1的未被重视的作用 抑制逆转肿瘤诱导的免疫抑制。

Project summary Tumors employ a number of mechanisms to promote immune escape, including the infiltration of different immunosuppressive cells in the tumor microenvironment such as T-regulatory cells (Treg). However, the specific signals within tumor cells that regulate the recruitment of Tregs, giving rise to tumor-induced immunosuppression, remain elusive. Based on our new preliminary data, we hypothesize that WEE1, an important regulator for cell cycle checkpoints, maintains an immunosuppressive and pro- tumorigenic microenvironment, and suppressing WEE1 activity, including via a clinically relevant WEE1 inhibitor, may be therapeutically beneficial by boosting immune-mediated tumor clearance. This proposal seeks to characterize the novel regulatory perspectives of WEE1-mediated crosstalk between tumor cells and host immune cells that should significantly forward the field. Specifically, this project is searching for the molecular mechanisms of WEE1-mediated Treg regulation and development of new effective combinatorial strategies. Our work will thus identify an unappreciated role of WEE1 inhibition in reversing tumor-induced immune suppression.