학술논문

Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment
Document Type
article
Source
Nature Communications. 12(1)
Subject
Cancer
Digestive Diseases
Rare Diseases
Human Genome
Genetics
Aetiology
2.1 Biological and endogenous factors
Antigen Presentation
Biomarkers
Tumor
Dendritic Cells
Esophageal Neoplasms
Esophageal Squamous Cell Carcinoma
Gene Expression Profiling
Gene Expression Regulation
Neoplastic
Histocompatibility Antigens Class II
Humans
Myeloid Cells
Myofibroblasts
Prognosis
Salivary Cystatins
Single-Cell Analysis
Survival Analysis
T-Lymphocytes
Tumor Microenvironment
Language
Abstract
The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1+ myofibroblasts with prognostic values and potential biological significance. CST1+ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.