Effect of immune infiltration intensity on the efficacy of neoadjuvant immunotherapy for esophageal cancer

TL;DR

This study shows that immune infiltration in esophageal cancer affects how well immunotherapy works, with certain genes like CXCL10 predicting better treatment outcomes.

Contribution

The study identifies specific genes linked to immune infiltration and treatment response in neoadjuvant immunotherapy for ESCC.

Findings

Patients with complete pathological response showed distinct gene expression related to immune cell activity.

CXCL10 and other genes were upregulated in tumor tissues and correlated with improved survival.

FAT1 was downregulated at the protein level in tumor tissues compared to normal tissues.

Abstract

Esophageal squamous cell carcinoma (ESCC) treatment often involves neoadjuvant therapy combining chemotherapy and immune checkpoint inhibitors. However, the effectiveness of these treatments is limited by immune infiltration in the tumor microenvironment.

We analyzed single-cell transcriptomic data from 22 patients with resectable ESCC, collected before and after neoadjuvant therapy. Differences in gene expression between patients achieving a complete pathological response (pCR) and those who did not were assessed. We further validated our findings using RNAseq data from The Cancer Genome Atlas (TCGA), and conducted quantitative qRT-PCR and Western blot analyses on tumor tissues from a clinical cohort.

Significant differences in gene expression related to T cell activation, natural killer cell activity, and cytokine signaling were observed between pCR and non-pCR patients. Notable genes included CXCL10, CXCL11, ME1, MT1X, FAT1, OAS2, and MT2A. TCGA data confirmed a correlation between high gene expression and increased tumor mutational burden as well as improved survival rates, particularly for CXCL10. qRT-PCR revealed significant upregulation of CXCL10, CXCL11, ME1, MT1X, FAT1, OAS2, and MT2A in tumor tissues compared to normal tissues. Western blot analysis showed increased protein levels of CXCL10, CXCL11, OAS2, MT1E, and MT1X, while FAT1 was downregulated.

Our study highlights the critical role of immune infiltration and associated molecular pathways in the efficacy of neoadjuvant immunotherapy for ESCC. Specific genes, such as CXCL10, are promising as predictive markers for treatment response and survival.

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