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A Functionally Constrained Immune Ecosystem in Microsatellite-stable Colorectal Cancer Resolved by Single-cell and Exome Profiling.

Wenxu Liu·Yipan Zheng·Hao Wang·Feng Qi·Xiulan Zhao·Zhenyi Ma·Zhe Liu
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Abstract

BACKGROUND/AIM: Microsatellite-stable (MSS) colorectal cancer (CRC) generally responds poorly to immune checkpoint blockade, but some MSS tumors are T-cell rich. We examined whether such infiltration reflected effective immunity or functional immune constraint. CASE REPORT: A 77-year-old woman underwent resection of a mismatch repair-proficient (pMMR), MSS, low-mutational-burden CRC with a synchronous adenoma. Whole-exome sequencing of tumor, adenoma and adjacent normal tissue detected no shared high-confidence somatic mutations between tumor and adenoma within the sensitivity of this WES analysis and identified tumor-specific APC, KRAS and TP53 alterations. Tumor single-cell RNA sequencing yielded 7,569 cells, with T-lineage populations comprising 83.5%. Cytotoxic T cells showed cytolytic and dysfunction-associated features, regulatory T cells (Tregs) showed suppressive remodeling, and Th17 cells showed inflammatory/profibrotic programs. CellChat nominated stromal MIF/FN1-CD74/CD44 and extracellular-matrix communication with T-cell compartments. CONCLUSION: This molecular case report shows that T-cell abundance and immune effectiveness can be uncoupled in MSS CRC.

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HumansFemaleAgedColorectal NeoplasmsExome SequencingSingle-Cell AnalysisMicrosatellite InstabilityMicrosatellite RepeatsT-Lymphocytes, RegulatoryMutationColorectal cancerFN1MIFTh17 cellscancer-associated fibroblastsmicrosatellite-stable colorectal cancerregulatory T cellssingle-cell RNA sequencingtumor microenvironmentwhole-exome sequencingJournal ArticleCase Reports

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Wenxu Liu, Yipan Zheng, Hao Wang, Feng Qi, Xiulan Zhao, Zhenyi Ma, Zhe Liu. 2026. A Functionally Constrained Immune Ecosystem in Microsatellite-stable Colorectal Cancer Resolved by Single-cell and Exome Profiling.. https://doi.org/10.21873/cgp.20615

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