Obesity enhances the response to neoadjuvant anti-PD1 therapy in oral tongue squamous cell carcinoma.

ABSTRACT

OBJECTIVES: Previous studies have demonstrated that obesity may impact the efficacy of anti-PD1 therapy, but the underlying mechanism remains unclear. In this study, our objective was to determine the prognostic value of obesity in patients with oral tongue squamous cell carcinoma (OTSCC) treated with pembrolizumab and establish a subtype based on fatty acid metabolism-related genes (FAMRGs) for immunotherapy. MATERIALS AND METHODS: We enrolled a total of 56 patients with OTSCC who underwent neoadjuvant anti-PD1 therapy. Univariate and multivariate Cox regression analyses, Kaplan-Meier survival analysis, and immunohistochemistry staining were performed. Additionally, we acquired the gene expression profiles of pan-cancer samples and conducted GSEA and KEGG pathway analysis. Moreover, data from TCGA, MSigDB, UALCAN, GEPIA and TIMER were utilized to construct the FAMRGs subtype. RESULTS: Our findings indicate that high Body Mass Index (BMI) was significantly associated with improved PFS (HR = 0.015; 95% CI, 0.001 to 0.477; p = 0.015), potentially attributed to increased infiltration of PD1 + T cells. A total of 91 differentially expressed FAMRGs were identified between the response and non-response groups in pan-cancer patients treated with immunotherapy. Of these, 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) were found to affect PD-1 expression and T cell infiltration in HNSCC, which may impact the efficacy of anti-PD1 therapy. CONCLUSION: This study demonstrates that obesity serves as a robust prognostic predictor for patients with OTSCC undergoing neoadjuvant anti-PD1 therapy. Furthermore, the expression of 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) plays a pivotal role in the context of anti-PD1 therapy and deserves further investigation.