Long-Term Prognosis and Immunotranscriptomic Landscape in Esophageal Squamous Cell Carcinoma With Different Pathological Responses to Neoadjuvant Chemoradiotherapy: A Retrospective Cohort Study

Abstract

Evidence is limited on long-term prognosis, and little is known about the immunotranscriptome in esophageal squamous cell carcinoma (ESCC) patients with different tumor regression grades (TRGs) after neoadjuvant chemoradiotherapy (NCRT) followed by surgery. Herein, the prognostic analysis of 300 ESCC patients treated with NCRT and surgery revealed that the TRG0/1 group (good responders) had significantly longer disease-free survival (DFS) and overall survival (OS) than the TRG2/3 group. Integrating TRG and pathological N-stage, we developed a tumor regression grade and lymph node (TRGN) staging system, which demonstrated superior prognostic stratification and distinct recurrence patterns. Transcriptome analysis showed that compared to the TRG2/3 group, the TRG0/1 group exhibited higher scores in immune checkpoint blockade (ICB) response-related signatures, greater similarity to ICB responder samples, and increased T-cell receptor clonality, suggesting enhanced immunotherapy sensitivity. Integrating scRNA-seq and RNA-seq, we identified B cell, CD8+ T cell, and NK cell subsets associated with better NCRT responses, within which a tight cell communication network potentially mediating antitumor immunity was formed. Multiplexed immunohistochemistry confirmed that the spatial relationship between CD8+ T/NK cells and tumor cells improved the NCRT response. These findings confirmed the prognostic value of TRGs and can help guide surveillance and treatment strategies in ESCC.

Keywords

esophageal squamous cell carcinoma / immunotranscriptome / neoadjuvant chemoradiotherapy / prognosis / tumor regression grades

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