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Updated: Sep 11, 2025
An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
Published on: July 20, 2014
Single-cell profiling identifies biomarkers for immunochemotherapy in esophageal squamous cell carcinoma
Changchun Wang1, Guanglei Xie2, Mingming Jia2
1Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China; Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology, Hangzhou, 310022, China.
Abstract:
Esophageal squamous cell carcinoma (ESCC) remains a highly aggressive malignancy with limited therapeutic options. While immune checkpoint blockade (ICB) combined with chemotherapy has improved outcomes, resistance mechanisms and predictive biomarkers are poorly understood. This study aims to characterize the dynamic changes in the tumor microenvironment (TME) during ICB treatment and identify cell populations and molecular programs associated with therapeutic response. We performed scRNA-seq, scTCR-seq, and scBCR-seq on 174,223 cells from 27 samples (22 paired pre- and post-treatment tumors, 2 unpaired tumors, and 3 adjacent tissues) treated with neoadjuvant camrelizumab (anti-PD-1) plus chemotherapy. ICB treatment reshaped the TME, increasing CXCL12+ inflammatory fibroblasts and CD1C+ dendritic cells while reducing neutrophils and plasma cells. Resistance-associated features included malignant cells with partial epithelial-mesenchymal transition (p-EMT) programs, DES+ myofibroblasts, FOLR2+ macrophages, and clonally expanded CD8+ T cells exhibiting terminal exhaustion. On the other hand, responders harbored more RGS13+ germinal center B cells. This study reveals the cellular and molecular reprogramming of the TME during ICB therapy and identifies biomarkers of response and resistance in ESCC. These insights could potentially guide patient stratification and the development of targeted strategies to overcome ICB resistance.
Insights
Immune checkpoint blockade (ICB) reshapes the tumor microenvironment in esophageal cancer. This study identifies specific cell changes and molecular programs linked to treatment response and resistance, offering potential biomarkers for patient stratification.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Esophageal squamous cell carcinoma (ESCC) is aggressive with limited treatments.
- Immune checkpoint blockade (ICB) plus chemotherapy improves outcomes but resistance is common.
- Biomarkers for ICB response in ESCC are poorly understood.
Purpose of the Study:
- To characterize dynamic tumor microenvironment (TME) changes during ICB therapy.
- To identify cell populations and molecular programs associated with therapeutic response and resistance.
- To discover biomarkers for patient stratification in ESCC.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq), TCR sequencing (scTCR-seq), and BCR sequencing (scBCR-seq) were performed.
- Analysis included 174,223 cells from 27 paired and unpaired tumor samples and adjacent tissues.
- Samples were from patients treated with neoadjuvant camrelizumab (anti-PD-1) and chemotherapy.
Main Results:
- ICB treatment altered the TME, increasing CXCL12+ fibroblasts and CD1C+ dendritic cells, while decreasing neutrophils and plasma cells.
- Resistance was associated with malignant cells showing partial epithelial-mesenchymal transition (p-EMT), DES+ myofibroblasts, FOLR2+ macrophages, and exhausted CD8+ T cells.
- Therapeutic response correlated with RGS13+ germinal center B cells.
Conclusions:
- ICB therapy induces significant cellular and molecular reprogramming of the ESCC TME.
- Specific cell populations and molecular programs serve as potential biomarkers for ICB response and resistance.
- Findings may guide patient stratification and strategies to overcome ICB resistance in esophageal cancer.
