FBW7-mediated ubiquitination and destruction of PD-1 protein primes sensitivity to anti-PD-1 immunotherapy in non-small cell lung cancer.
Jiaxin LiuLingyun WeiNan HuDong WangJuan NiSha ZhangHongbing LiuTangfeng LvJie YinMingxiang YeYong SongPublished in: Journal for immunotherapy of cancer (2022)
This study highlights the critical role of FBW7 in determining PD-1 protein stability. FBW7 ubiquitinates PD-1 in a phosphorylation-dependent manner, as a consequence, leading to PD-1 protein degradation and cytotoxic lymphocytes infiltrating the tumor microenvironment. Screening FBW7 status would predict clinical response to anti-PD-1 immunotherapy in patients with NSCLC, and targeting FBW7 is a promising strategy to enhance antitumor immunity.