Abrogation of USP7 is an alternative strategy to downregulate PD-L1 and sensitize gastric cancer cells to T cells killing

• DOI: 10.1016/j.apsb.2020.11.005
• Publication Date: 2020-11-16T16:49:31Z
• Authors: Zhiru Wang; Wenting Kang; Ouwen Li; Fengyu Qi; Junwei Wang; Yinghua You; Pengxing He; Zhenhe Suo; Yichao Zheng; Hong-Min Liu
• Keywords: Cancer Immunotherapy; Immune checkpoint

Targeting immune checkpoints such as programmed cell death protein 1 (PD-1) and ligand-1 (PD-L1) have been approved for treating melanoma, gastric cancer (GC) bladder with clinical benefit. Nevertheless, many patients failed to respond anti-PD-1/PD-L1 treatment, so it is necessary seek an alternative strategy traditional PD-1/PD-L1 targeting immunotherapy. Here the data from The Cancer Genome Atlas (TCGA) our in-house tissue library, PD-L1 expression was found be positively correlated of ubiquitin-specific processing protease 7 (USP7) in GC. Furthermore, USP7 directly interacted order stabilize it, while abrogation attenuated PD-L1/PD-1 interaction sensitized cells T killing vitro vivo. Besides, inhibitor suppressed GC proliferation by stabilizing P53 Collectively, findings indicate that addition inhibiting proliferation, can also downregulate enhance anti-tumor response simultaneously. Hence, these posit anti-proliferation agent well a novel therapeutic blockade promote tumor.