Efficacy of Neoadjuvant Chemotherapy Combined with Anti-PD-1 Monoclonal Antibody in Locally Advanced Resectable Oral Squamous Cell Carcinoma: A Single-Arm Phase II Clinical Trial

Background: Neoadjuvant chemotherapy (NAC) combined with anti-PD-1 antibody is a potential treatment option for resectable oral squamous cell carcinoma (OSCC). It is important to be able to predict the effectiveness of NAC combined with anti-PD-1 antibody in clinical practice. Methods: In total, 30 patients with locally advanced, resectable OSCC (T3–T4, N0–N2, M0) who received two cycles of neoadjuvant chemoimmunotherapy (NACI) consisting of albumin-bound paclitaxel (250 mg/m2) and cisplatin (75 mg/m2) with the anti-PD-1 monoclonal antibody sintilimab (200 mg) were enrolled in this single-arm phase II trial. Twenty-three patients underwent surgical resection and seven received nonsurgical therapy. The primary and secondary end points were pathological response and clinical response, respectively. We utilized artificial intelligence (AI)-powered nuclear segmentation and classification to preliminarily assess the level of inflammatory cell infiltration in patients before NACI. Transcriptome RNA sequencing (RNA-seq) analysis was used to identify differentially expressed genes and immune cell subtypes between patients with and without major pathological response (MPR). Results: The MPR rate was 39.1% among 23 patients who underwent surgical resection. The objective response rate (ORR) was 43.3%. The primary location of OSCC was associated with the pathological response. There were no significant differences in the overall level of inflammatory cell infiltration between patients with and without MPR. Immune infiltration analysis of RNA-seq data revealed significant differences in the proportions of M1- and M2-type macrophages between the MPR and non-MPR groups. Conclusions: This study reveals the potential efficacy of NAC combined with anti-PD-1 antibody in treating OSCC patients, with acceptable side effects. This strategy can effectively inhibit clinical progression of locally advanced OSCC. The pathological response may be related to the degree of M1 macrophage infiltration.