Related Experiment Video
Updated: Jun 10, 2026
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Establishment and multi-omics characterization of a PD-1-resistant murine esophageal squamous cell carcinoma cell
Yi Xu1, Xianhao Wang1, Yujiao Sun2
1Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, 215008, China.
Abstract:
Immunotherapy has revolutionized the treatment of esophageal squamous cell carcinoma (ESCC), but its clinical application is limited by low response rates and acquired resistance. The exploration of underlying is hampered by the absence of preclinical models that faithfully recapitulate the immune microenvironment and drug-resistant features of ESCC. Here, we established a novel murine ESCC cell line named mESCC-030, which was derived from primary ESCC tumors induced by 4-Nitroquinoline N-oxide (4-NQO) in C57BL/6 mice via consecutive in vivo selection. This cell line was validated by morphological observation and STR identification. Compared with primary parental cells, mESCC-030 exhibits stronger malignant proliferation, invasion and migration capabilities, and achieves 100% subcutaneous tumorigenicity in C57BL/6 mice. Moreover, the syngeneic graft tumors derived from this cell line display prominent resistance to PD-1 antibody therapy. Bulk transcriptomic profiling revealed that this cell line harbors enhanced proliferation-related pathways and diminished immune response pathways. Single-cell RNA sequencing of graft tumors identified a highly proliferative cell cluster in tumor tissues, along with an extremely low proportion of immune infiltrating cells. Taken together, the mESCC-30 cell line and its syngeneic tumors represent a typical immune-cold tumor model, providing a novel platform to uncover immunotherapy resistance mechanisms and develop combination therapeutic strategies.
Insights
A new mouse model for esophageal squamous cell carcinoma (ESCC) was developed to study immunotherapy resistance. This model exhibits immune-cold features, offering a platform for exploring resistance mechanisms and combination therapies.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Immunotherapy has transformed esophageal squamous cell carcinoma (ESCC) treatment but faces challenges with low response rates and resistance.
- Preclinical models that accurately reflect ESCC's immune microenvironment and drug resistance are lacking, hindering research.
- Developing reliable models is crucial for advancing ESCC immunotherapeutic strategies.
Purpose of the Study:
- To establish a novel preclinical model for esophageal squamous cell carcinoma (ESCC) that mimics immune resistance.
- To characterize the biological and immunological features of the new model.
- To provide a platform for investigating immunotherapy resistance mechanisms in ESCC.
Main Methods:
- A new murine ESCC cell line (mESCC-030) was generated from 4-Nitroquinoline N-oxide-induced tumors in C57BL/6 mice through in vivo selection.
- Morphological observation and Short Tandem Repeat (STR) identification were used for cell line validation.
- Subcutaneous tumorigenicity, transcriptomic profiling, and single-cell RNA sequencing were employed to analyze tumor characteristics and immune infiltration.
Main Results:
- The mESCC-030 cell line demonstrated enhanced malignant proliferation, invasion, and migration compared to parental cells.
- Syngeneic graft tumors from mESCC-030 exhibited significant resistance to PD-1 antibody therapy.
- Transcriptomic analysis revealed upregulated proliferation pathways and downregulated immune response pathways, consistent with an immune-cold phenotype.
- Single-cell RNA sequencing identified a highly proliferative cell cluster and a very low proportion of immune-infiltrating cells in graft tumors.
Conclusions:
- The mESCC-030 cell line and its derived syngeneic tumors represent a valuable immune-cold ESCC model.
- This model provides a novel platform for uncovering mechanisms of immunotherapy resistance in ESCC.
- It facilitates the development and testing of combination therapeutic strategies for resistant ESCC.
More Related Videos
05:57Establishment and Histological Analysis of Esophageal Organoids Modeling the Progression from Normal to Cancerous Tissues
Published on: May 30, 2025
07:29Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019