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Related Experiment Video

Updated: Apr 5, 2026

Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
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Integrated single‑cell and spatial transcriptomics reveal the colorectal cancer microenvironment.

Ruihan Yang1, Shijia Hu2, Kaifan Li3

  • 1School of Basic Medical Sciences, Henan Medical University, Xinxiang, Henan Province 453003, China.

Critical Reviews in Oncology/Hematology
|April 4, 2026
PubMed
Summary

Single-cell sequencing and spatial transcriptomics reveal complex colorectal cancer (CRC) ecosystems. These technologies identify key cellular interactions and pathways driving metastasis and immune evasion, offering new therapeutic targets for CRC.

Keywords:
Colorectal cancerImmunotherapySingle-cell sequencingSpatial transcriptomicsTumor microenvironment

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Area of Science:

  • Oncology
  • Genomics
  • Immunology
  • Bioinformatics

Background:

  • Colorectal cancer (CRC) presents significant global health challenges due to high incidence and mortality.
  • Understanding the intricate tumor microenvironment (TME) and cellular heterogeneity is crucial for developing effective CRC treatments.

Purpose of the Study:

  • To review the integrated application of single-cell sequencing and spatial transcriptomics in colorectal cancer research.
  • To elucidate the spatial organization of tumor-stroma-immune networks within the CRC TME.
  • To identify novel biomarkers and therapeutic targets for CRC based on advanced multi-omics data.

Main Methods:

  • Integration of single-cell sequencing to analyze cellular heterogeneity and interaction networks.
  • Application of spatial transcriptomics to map cellular distribution and tissue architecture within the CRC TME.
  • Analysis of spatially organized tumor-stroma-immune networks, including immune-excluded, immune-active, and tertiary lymphoid structure (TLS) domains.

Main Results:

  • Detailed mapping of spatially organized tumor-stroma-immune networks, revealing immune-excluded zones (CAF-mediated ECM barriers, SPP1⁺ TAMs) and immune-active niches (T cell-myeloid cooperation).
  • Identification of MGP-high epithelial cells driving liver metastasis via PD-L1 upregulation and SPP1⁺ CAFs contributing to immunosuppressive metastatic niches.
  • Functional validation of mechanisms including IL1R1⁺ iCAFs promoting M2 polarization and MDK-SDC4 interactions facilitating Treg migration.

Conclusions:

  • Integrated single-cell and spatial transcriptomics provide unprecedented insights into CRC biology and the TME.
  • Key findings highlight specific cell populations (e.g., SPP1⁺ CAFs, IL1R1⁺ iCAFs) and molecular axes (e.g., MDK-SDC4) as potential diagnostic biomarkers and therapeutic targets.
  • This approach advances precision diagnostics and therapeutics, offering a framework for future CRC research and clinical practice.