Influence of high COL19A1 expression on the effectiveness of neoadjuvant immunotherapy plus chemotherapy and long-term survival in patients with esophageal squamous cell carcinoma

e16013 Background: Neoadjuvant immunotherapy plus chemotherapy may enhance the resectability rate in locally advanced Esophageal Squamous Cell Carcinoma (ESCC). Nevertheless, due to the complex nature of the tumor immune microenvironment, an unmet need remains for biomarkers to identify NPC patients used to identify patients who benefit most from this neoadjuvant treatment strategy. Methods: Two independent cohorts of ESCC patients were enrolled in the study., including retrospective cohort (N=66) and prospective cohort (N=37). A total of 103 NPC FFPE samples were subjected to RNA sequencing. Single sample GSEA (ssGSEA) were performed to explore the Tumor microenvironment (TME). Differential genes associated with survival were analyzed using logistic regression and Kaplan-Meier methods. To reveal the expression of biomarker and TME, immunohistochemistry and multiplex immunofluorescence were used. Results: We demonstrated that COL19A1 high expression facilitates anti-PD-1 therapy [ COL19A1 high, OR (95% CI): 0.31 (0.1−0.97), p = 0.044]. COL19A1 high patients could benefit more from neoadjuvant immunotherapy (p < 0.01), high mortality (63.3%, p < 0.01), and have a trend towards a better RFS (p = 0.13) and OS (p = 0.056). Further analyses confirmed increased B cells infiltration and COL19A1 high expression could be seen in the immune-activated subgroup, which resulted in favorable survival and response to neoadjuvant immunotherapy plus chemotherapy. Conclusions: This study revealed an ESCC subpopulation presenting high COL19A1 expression, which responded well to neoadjuvant immunotherapy plus chemotherapy and was associated with good prognosis. It provided a convincing basis for designing biomarker-guided individual treatment.