COL19A1 is a predictive biomarker for the responsiveness of esophageal squamous cell carcinoma patients to immune checkpoint therapy

Abstract

Abstract Background The use of neoadjuvant immunotherapy plus chemotherapy has revolutionized the management of esophageal squamous cell carcinoma (ESCC) patients. Nevertheless, patients who would maximally benefit from these therapies have not been identified. Methods We collected postoperative specimens from 103 ESCC patients, of which 66 patients comprised a retrospective cohort and 37 comprised a prospective cohort. Patient specimens were subjected to applied multi‐omics analysis to uncover the mechanistic basis for patient responsiveness to cancer immunotherapy. The tumor microenvironment characteristics of these patient specimens was explored and identified by multiplex immunofluorescence and immunohistochemistry. Results Results demonstrated high COL19A1 expression to be a novel biomarker for successful immunotherapy (COL19A1high, odds ratio [95% confidence interval]: 0.31 [0.10–0.97], p = 0.044). Compared with COL19A1low patients, COL19A1high patients benefited more from neoadjuvant immunotherapy (p < 0.01), obtained better major pathological remissions (63.3%, p < 0.01), with a trend toward better recurrence‐free survival (p = 0.013), and overall survival (p = 0.056). Moreover, analysis of an immune‐activation subtype of patients demonstrated increased B cell infiltration to be associated with favorable patient survival and a better response to neoadjuvant immunotherapy plus chemotherapy. Conclusions The findings of this study provide insight into the optimal design of individual treatments for ESCC patients.

Keywords

• B cell infiltration
• COL19A1
• esophageal squamous cell carcinoma
• neoadjuvant immunotherapy