Correlation of immune cell subsets in the tumor microenvironment and peripheral blood with immunotherapy response in esophageal squamous cell carcinoma

TL;DR

This study identifies TIM3+ CD8+ T cells as a potential biomarker for predicting immunotherapy response in esophageal squamous cell carcinoma.

Contribution

The study introduces TIM3+ CD8+ T cell changes in peripheral blood as a novel predictive biomarker for immunotherapy outcomes in ESCC.

Findings

TIM3+ CD8+ T cells in peripheral blood showed significant changes following immunotherapy.

Patients with higher TIM3+ CD8+ T cell changes had shorter progression-free survival.

TIM3+ CD8+ T cell changes were reduced in patients with positive treatment responses.

Abstract

Esophageal squamous cell carcinoma (ESCC) is commonly diagnosed at an advanced stage, where conventional chemoradiotherapy offers only limited clinical benefit. Immune checkpoint inhibitors targeting the tumor microenvironment (TME) have demonstrated substantial therapeutic potential; however, reliable biomarkers for predicting therapeutic outcomes remain unclear.

Single-cell RNA sequencing dataset for ESCC was obtained from the GEO database and analyzed using the Seurat R package to evaluate gene expression in tumor and adjacent tissues. Additionally, flow cytometry was used to assess immune cell subsets in peripheral blood samples from patients undergoing immunotherapy. Statistical analyses, including survival analysis and the Kruskal-Wallis test, were conducted to investigate the association between immune cell subsets and treatment efficacy.

In tumor tissues, immune subsets were significantly enriched compared with adjacent tissues, including CD8+ T cells with exhaustion (CD39, TIM3, PD-1) or activation/tissue residency (CD137, CD103) features; CD4+ T cells with activation (CD134, CD137) or regulatory (FOXP3) phenotypes; and dendritic cells expressing TIM3 or CD103. In peripheral blood, a median change in TIM3+ CD8+ T cells of 3.35% was observed following immunotherapy. Patients with changes exceeding this threshold experienced shorter progression-free survival (PFS) compared to those with lower changes (5.0 vs. 8.5 months, P = 0.024). Furthermore, TIM3+ CD8+ T cell changes were markedly reduced in patients achieving complete or partial responses compared to those with progressive disease.

TIM3+ CD8+ T cells are a promising predictive biomarker for immunotherapy outcomes in ESCC. These findings highlight their potential to guide personalized treatment strategies in clinical practice.

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