High-dimensional single-cell proteomics analysis of esophageal squamous cell carcinoma reveals dynamic alterations of the tumor immune microenvironment after neoadjuvant therapy

Dingpei Han, Yichao Han, Wei Guo, Wei Wei, Su Yang, Jie Xiang, Jiaming Che, Lianggang Zhu, Junbiao Hang, Tom van den Ende, Hanneke W. M. van Laarhoven, Bin Li, Youqiong Ye, Hecheng Li

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3 Citations (Scopus)

Abstract

Background Dynamic alterations of the tumor immune microenvironment in esophageal squamous cell carcinoma (ESCC) after different neoadjuvant therapies were understudied. Methods We used mass cytometry with a 42-antibody panel for 6 adjacent normal esophageal mucosa and 26 tumor samples (treatment-naïve, n=12; postneoadjuvant, n=14) from patients with ESCC. Single-cell RNA sequencing of previous studies and bulk RNA sequencing from The Cancer Genome Atlas were analyzed, flow cytometry, immunohistochemistry, and immunofluorescence analyses were performed. Results Poor tumor regression was observed in the neoadjuvant chemotherapy group. Radiotherapy-based regimens enhanced CD8 + T cells but diminished regulatory T cells and promoted the ratio of effector memory to central memory T cells. Immune checkpoint blockade augmented NK cell activation and cytotoxicity by increasing the frequency of CD16 + NK cells. We discovered a novel CCR4 + CCR6 + macrophage subset that correlated with the enrichment of corresponding chemokines (CCL3/CCL5/CCL17/CCL20/CCL22). We established a CCR4/CCR6 chemokine-based model that stratified ESCC patients with differential overall survival and responsiveness to neoadjuvant chemoradiotherapy combined with immunotherapy, which was validated in two independent cohorts of esophageal cancer with neoadjuvant treatment. Conclusions This work reveals that neoadjuvant therapy significantly regulates the cellular composition of the tumor immune microenvironment in ESCC and proposes a potential model of CCR4/CCR6 system to predict the benefits from neoadjuvant chemoradiotherapy combined with immunotherapy.
Original languageEnglish
Article numbere007847
JournalJournal for Immunotherapy of Cancer
Volume11
Issue number11
DOIs
Publication statusPublished - 28 Nov 2023

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