Neoadjuvant chemotherapy combined with anti-PD-1 monoclonal antibody in locally advanced resectable oral squamous cell carcinoma: efficacy evaluation and prediction.

[BACKGROUND] Neoadjuvant chemotherapy (NAC) combined with anti-PD-1 antibody therapy is a potential treatment option for resectable oral squamous cell carcinoma (OSCC). Identifying biomarkers to predict therapeutic efficacy remains critical for optimizing this regimen.

[METHODS] Thirty patients with locally advanced, resectable OSCC (T3-T4, N0-N2, M0) who received two cycles of neoadjuvant chemoimmunotherapy (NACI) consisting of paclitaxel (175 mg/m) and cisplatin (75 mg/m) plus the anti-PD-1 monoclonal antibody sintilimab (200 mg) were enrolled in this single-arm phase II trial. Twenty-five patients underwent surgical resection and five received nonsurgical therapy. The primary and secondary end points were pathological response and clinical response, respectively. AI-powered nuclear segmentation and classification was applied to pre-treatment biopsy samples to spatially map inflammatory cell infiltration. Transcriptome RNA sequencing (RNA-seq) analysis and IHC were used to identify differentially expressed genes and immune cell subtypes between patients with and without major pathological response (MPR).

[RESULTS] The MPR rate was 44.0 % among the 25 patients who underwent surgical resection. The objective response rate (ORR) was 53.3 %. The primary tumor location significantly correlated with pathological response (P < 0.05). While AI analysis showed no significant difference in overall inflammatory cell infiltration between groups, immune infiltration analysis of the RNA-seq data revealed significant differences in the proportions of M1- and M2-type macrophages between the MPR and non-MPR groups. CD86 IHC validation across all 12 sequenced patients confirmed significantly elevated M1 infiltration in MPR tumors (13.75 % vs. 4.5 % CD86 cells, P < 0.001), directly linking M1 polarization to therapeutic sensitivity to PD-1 inhibition.

[CONCLUSIONS] NAC combined with anti-PD-1 antibody therapy demonstrates clinically meaningful efficacy in OSCC, accompanied by a manageable toxicity profile. M1 macrophage infiltration, validated by both RNA-seq and IHC, emerges as a novel predictive biomarker for pathological response, providing mechanistic insight into PD-1 blockade efficacy within the tumor microenvironment.

[TRIAL REGISTRATION] Chinese clinical trial registry, ChiCTR2400091891.