OTUD1 downregulates PD-L1 expression by deubiquitinating STAT3 and promotes the immune response in ccRCC

Renal cell carcinoma (RCC) is a common urinary malignancy. It has the highest mortality rate among urologic malignancies, and its incidence has been increasing in recent years, and its common subtype is renal clear cell carcinoma (ccRCC). Ovarian tumor domain protease 1 (OTUD1) is known as a member of the OTUD deubiquitinase family and has the ability to remove ubiquitin modifications from target proteins. The OTUD family consists of 10 members, including OTUD1, all of which have the function of deubiquitinating target proteins. In this study, we determined the correlation between OTUD1 and the immune pathway through bioinformatics analysis. Subsequently, by mass spectrometry analysis and immunoprecipitation experiments, we demonstrated that OTUD1 can interact with STAT3 and regulate the expression of PD-L1 in kidney cancer cells through STAT3. OTUD1 can also inhibit the activity and nuclear translocation of STAT3 by regulating the K63 ubiquitination modification of STAT3. Finally, we found that OTUD1 can deubiquitinate STAT3 and inhibit its activity and nuclear translocation, thereby regulating the PD-1 signaling pathway, and ultimately promoting the immune response of renal cancer tumors.