WEE1 inhibition and tumor immunity

项目总结 肿瘤使用许多机制来促进免疫逃逸，包括 不同免疫抑制细胞在肿瘤微环境中的渗透 T-调节细胞(Treg)。然而，调节肿瘤细胞内的特定信号 导致肿瘤免疫抑制的Tregs的招募仍然存在 难以捉摸。根据我们新的初步数据，我们假设WEE1，一个重要的 细胞周期检查点的调节器，维持免疫抑制和促进 致瘤微环境，以及抑制WEE1活性，包括通过临床 相关的WEE1抑制剂，可能通过促进免疫介导的治疗而受益 肿瘤清除。这项提议试图描述新的监管视角。 WEE1介导的肿瘤细胞和宿主免疫细胞之间的串扰 在场上向前推进。具体地说，这个项目是在寻找分子 WEE1介导的Treg调节机制及新效应的研究进展 组合策略。因此，我们的工作将确定WEE1未被重视的角色 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.