CFD overexpression inhibits CESC progression and enhances TIL therapy efficacy via NOSTRIN and eNOS signaling pathway.

Source: PubMed, NCBI / U.S. National Library of Medicine

Cervical squamous cell carcinoma (CESC) represents the second most commonly diagnosed malignancy among women worldwide, with substantial incidence and mortality rates, particularly in regions where breast cancer is not predominant. Recent advances in tumor-infiltrating lymphocyte (TIL) therapy have demonstrated promising clinical efficacy in CESC. This study elucidated the role of complement factor D (CFD) in CESC and evaluated its potential as a therapeutic target. Bioinformatic analysis of the GSE39001 dataset revealed significant downregulation of CFD in CESC tissues, a finding subsequently validated in 43 paired tumor and adjacent normal tissue samples. Functional assays demonstrated that CFD overexpression in CESC cell lines (SiHa and C33A) substantially suppressed cell proliferation, viability, and invasion, while concurrently attenuating CD8 + T cell exhaustion. Mechanistically, CFD overexpression upregulated nitric oxide synthase trafficking inducer (NOSTRIN) and suppressed the endothelial nitric oxide synthase (eNOS) signaling pathway, as confirmed through RNA sequencing and co-immunoprecipitation assays. Furthermore, the combination of TIL therapy with CFD overexpression significantly suppressed tumor growth in a PDX model. These findings identify CFD as a potential therapeutic target for CESC and suggest that CFD overexpression may enhance the efficacy of TIL therapy in this malignancy.