GMPS promotes cervical squamous cell carcinoma cell immune evasion through USP7-mediated deubiquitination of PDL1.

Cervical squamous cell carcinoma (CSCC) is the most common subtype of cervical cancer (CC), which is a gynecological malignancy with poor survival. Immunotherapy is a promising approach to anti-CC. GMPS has been found to promote CC cell proliferation and inhibit apoptosis; however, whether it regulates immune evasion remains unknown. This study aimed to investigate the role of GMPS in CSCC and the molecular mechanism. In vitro experiments were performed to analyze cell proliferation and immune evasion, while in vivo experiments were conducted to assess the impact of GMPS on tumor growth and immune evasion. The results showed that GMPS expression was increased in CC tissues and cells. Knockdown of GMPS suppressed CSCC cell proliferation, enhanced the toxicity and activity of CD8+ T cells, suppressed the apoptosis of CD8+ T cells, and reduced the protein levels of PDL1. Moreover, silencing of GMPS inhibited xenograft tumor growth and suppressed immune evasion in immune-competent mice. Additionally, GMPS interacted with USP7 and positively regulated USP7 expression, and overexpression of USP7 abrogated the inhibition of cell proliferation and immune evasion mediated by GMPS knockdown. We also found that silencing of USP7 inhibited PDL1 protein stability via an increase in ubiquitination levels. In conclusion, GMPS accelerates CSCC progression by promoting cell proliferation and immune evasion. Mechanistically, GMPS interacts with USP7, which promotes the deubiquitination of PDL1. These findings provide new ideas for the immune escape mechanism of CSCC and indicate that GMPS is a promising target for immunotherapy.