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Updated: Jul 16, 2026
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Dissociation of Human and Mouse Tumor Tissue Samples for Single-cell RNA Sequencing
Published on: August 16, 2024
Dissecting immunosuppressive microenvironment in chemotherapy-resistant colorectal cancer through single-cell
Jinchuan Xi1, Zhihan Li1, Youqiang Liu1
1The Second Department of Surgery, The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Shijiazhuang City, Hebei Province, 050000, China.
Translational Oncology
|July 14, 2026
Summary
Chemotherapy resistance in colorectal cancer is driven by an immunosuppressive tumor microenvironment. Single-cell analysis reveals TME remodeling, identifying immune evasion mechanisms and potential therapeutic targets for combination immunotherapy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Colorectal cancer (CRC) is a major cause of cancer mortality.
- Chemotherapy resistance is a significant treatment challenge.
- The tumor microenvironment (TME) influences chemotherapy resistance through immunosuppression.
Purpose of the Study:
- To comprehensively analyze the TME in chemotherapy-resistant CRC at single-cell resolution.
- To identify cellular and molecular mechanisms driving immune evasion in resistant CRC.
- To uncover potential therapeutic vulnerabilities for overcoming resistance.
Main Methods:
- Single-cell RNA sequencing of 13,380 cells from CRC specimens.
- Bioinformatic analyses including clustering, annotation, differential expression, and trajectory inference.
- In vitro validation using chemotherapy-resistant cell lines with RT-PCR and ELISA.
Main Results:
- Resistant tumors show altered TME composition (decreased cytotoxic cells, increased regulatory T cells/M2 macrophages).
- Suppressed T cell activation pathways and upregulated immunosuppressive programs (hypoxia, angiogenesis, metabolism).
- Enhanced inhibitory cell-cell communication (PD-L1/PD-1, CTLA-4, TGF-β, IL-10) and immune checkpoint molecule expression.
Conclusions:
- Single-cell analysis reveals a multi-dimensional immunosuppressive landscape in chemotherapy-resistant CRC.
- Identified coordinated cellular, molecular, and spatial mechanisms driving immune evasion.
- Findings provide biomarkers for resistance prediction and highlight targets for immunotherapy combination strategies.
