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.