Tumor immune microenvironment remodeling and prognosis of patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy with and without immunotherapy

Abstract Objective This study investigated the outcomes of neoadjuvant chemotherapy with and without immunotherapy in tumor microenvironment (TME) remodeling among patients with esophageal squamous cell carcinoma (ESCC) . Methods Retrospectively reviewed the data of patients with ESCC who received neoadjuvant chemotherapy, with or without immunotherapy (nCT and nICT groups, respectively), from December 2019 to March 2022 in the Fourth Hospital of Hebei Medical University. Histopathology specimens of cancer tissue before and after treatment were examined for TME features. Results A total of 50 patients underwent R0 resection, with rates of pathological complete response (pCR) and major pathological response (MPR) of 18% and 30%, respectively. Rates of pCR were 7.1% and 22.2% (P = 0.403) and those of MPR were 7.1% and 38.9% (P = 0.028) in the nCT and nICT groups, respectively. The pCR patients had a higher baseline programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) positive expression rate than non-pCR patients (16.7% vs. 77.8%, P < 0.001). Comparing TME features before and after neoadjuvant treatment, an increase in PD-L1, CD3+ T cells, and CD8+ T cells in the tumor tissue were observed after neoadjuvant treatment, with more significantly increased in the nICT group than in the nCT group (P < 0.05). Cox regression analysis showed that pre-treatment well-differentiated tumors and positive PD-L1 were favorable factors for MPR. Post-treatment MPR was an independent factor affecting disease-free survival. Conclusion Neoadjuvant therapy could upregulate the PD-L1 expression level, increase tumor-infiltrating lymphocytes, and remodel the TME in patients with ESCC. Pre-treatment tumor differentiation and PD-L1 level could predict pathological remission.