Immunological biomarkers and predictive model for recurrence of esophageal squamous cell carcinoma after combined immunotherapy and neoadjuvant chemotherapy

Objective: To investigate the association between preoperative immunological biomarkers and risk of esophageal squamous cell carcinoma (ESCC) recurrence within 3 years after combined immunotherapy and neoadjuvant chemotherapy.

Methods: This retrospective case-control study included 348 ESCC patients who received immunotherapy and neoadjuvant chemotherapy in Henan Provincial People's Hospital between 2021 and 2023. Patients were divided into a recurrence (n=197) group and a non-recurrence (n=151) group based on their recurrence within 3 years. Tumor-infiltrating lymphocytes, serum tumor-specific antibodies, immune checkpoint expression, and HLA expression were analyzed and compared between groups. Correlation and regression analyses evaluated associations between biomarkers and recurrence risk. Then, a joint prediction model was established.

Results: The study revealed that CD8+ and Perforin+ cell percentages were significantly associated with a lower risk of recurrence (P<0.001), while EGFR, HER2, p53, PD-L1, CTLA-4, Tim-3, and LAG-3 were linked to an increased risk of recurrence (P<0.001). Lifestyle factors like salted food consumption, regular hot drink intake, gastric atrophy, and vitamin A deficiency also contributed to ESCC recurrence prediction (all P<0.05). A predictive model incorporating immune markers and risk factors for predicting ESCC recurrence within three years post-treatment demonstrated an AUC of 0.986.

Conclusion: Immunological biomarkers, including tumor-infiltrating lymphocytes, serum tumor antibodies, immune checkpoint expression, and HLA expression are associated with ESCC recurrence risk within 3 years of combined immunotherapy and neoadjuvant chemotherapy. These biomarkers may help stratify patients and guide management decisions.