---
title: "Immune Constraint in Microsatellite-Stable Colorectal Cancer Revealed by Single-Cell and Exome Pro"
id: "pubmed-42674816"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42674816"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42674816/"
doi: "10.21873/cgp.20615"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Immune Constraint in Microsatellite-Stable Colorectal Cancer Revealed by Single-Cell and Exome Pro
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42674816
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42674816/)
- **DOI:** [10.21873/cgp.20615](https://doi.org/10.21873%2Fcgp.20615)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Case report of a 77-year-old woman with a mismatch repair–proficient, **microsatellite-stable (MSS)** colorectal cancer (CRC) that had a low tumor mutational burden and a synchronous adenoma. Whole-exome sequencing (WES) detected tumor-specific alterations in **APC**, **KRAS**, and **TP53**, and no shared high-confidence somatic mutations between the tumor and the adenoma within the sensitivity of the WES analysis. - Tumor single-cell RNA sequencing recovered 7,569 cells, of which **T-lineage populations comprised 83.5%** of cells, indicating high T-cell abundance within this MSS CRC specimen. - Despite high T-cell infiltration, cytotoxic T cells expressed both **cytolytic** and **dysfunction-associated** transcriptional features, suggesting impaired effector capacity alongside cytolytic programs. - Regulatory T cells (Tregs) displayed evidence of **suppressive remodeling**, consistent with an immunosuppressive tumor microenvironment despite T-cell richness. - Th17-lineage cells exhibited **inflammatory and profibrotic** transcriptional programs, indicating proinflammatory stromal interactions that may affect tumor immunity. - Intercellular signaling analysis (CellChat) nominated stromal-to-immune communications including **MIF/FN1–CD74/CD44** and extracellular-matrix interactions between cancer-associated fibroblasts and T-cell compartments, implicating stromal pathways in constraining immune function. - The case demonstrates that **T-cell abundance and immune effectiveness can be uncoupled** in MSS CRC: a T-cell–rich infiltrate does not necessarily equate to effective anti-tumor immunity in mismatch repair–proficient disease. - Keywords highlighted by the authors include colorectal cancer, **FN1**, **MIF**, Th17 cells, cancer-associated fibroblasts, regulatory T cells, single-cell RNA sequencing, tumor microenvironment, and whole-exome sequencing.
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China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#full-view-affiliation-2 "School of Basic Medical Sciences, Central South University, Changsha, P.R. China."), [Yipan Zheng](https://pubmed.ncbi.nlm.nih.gov/?term=Zheng+Y&cauthor_id=42674816)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#full-view-affiliation-1 "Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China."), [Hao Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+H&cauthor_id=42674816)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#full-view-affiliation-3 "Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, P.R. China."), [Feng Qi](https://pubmed.ncbi.nlm.nih.gov/?term=Qi+F&cauthor_id=42674816)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#full-view-affiliation-4 "Tianjin Medical University General Hospital, Tianjin, P.R. China."), [Xiulan Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+X&cauthor_id=42674816)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#full-view-affiliation-5 "Department of Pathology, Tianjin Medical University, Tianjin, P.R. China."), [Zhenyi Ma](https://pubmed.ncbi.nlm.nih.gov/?term=Ma+Z&cauthor_id=42674816)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#full-view-affiliation-1 "Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China."), [Zhe Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+Z&cauthor_id=42674816)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#full-view-affiliation-6 "Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China; zheliu@hznu.edu.cn.") Affiliations Expand ### Affiliations * 1 Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China. * 2 School of Basic Medical Sciences, Central South University, Changsha, P.R. China. * 3 Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, P.R. China. * 4 Tianjin Medical University General Hospital, Tianjin, P.R. China. * 5 Department of Pathology, Tianjin Medical University, Tianjin, P.R. China. * 6 Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China; zheliu@hznu.edu.cn. * PMID: **42674816** * DOI: [ 10.21873/cgp.20615 ](https://doi.org/10.21873/cgp.20615) Item in Clipboard Case Reports # A Functionally Constrained Immune Ecosystem in Microsatellite-stable Colorectal Cancer Resolved by Single-cell and Exome Profiling Wenxu Liu et al. Cancer Genomics Proteomics. 2026 Sep-Oct. Show details Display options Display options Format Abstract PubMed PMID Cancer Genomics Proteomics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cancer+Genomics+Proteomics%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Cancer+Genomics+Proteomics%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42674816/) . 2026 Sep-Oct;23(5):1043-1060. doi: 10.21873/cgp.20615. ### Authors [Wenxu Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+W&cauthor_id=42674816)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#short-view-affiliation-1 "Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#short-view-affiliation-2 "School of Basic Medical Sciences, Central South University, Changsha, P.R. China."), [Yipan Zheng](https://pubmed.ncbi.nlm.nih.gov/?term=Zheng+Y&cauthor_id=42674816)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#short-view-affiliation-1 "Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China."), [Hao Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+H&cauthor_id=42674816)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#short-view-affiliation-3 "Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, P.R. China."), [Feng Qi](https://pubmed.ncbi.nlm.nih.gov/?term=Qi+F&cauthor_id=42674816)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#short-view-affiliation-4 "Tianjin Medical University General Hospital, Tianjin, P.R. China."), [Xiulan Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+X&cauthor_id=42674816)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#short-view-affiliation-5 "Department of Pathology, Tianjin Medical University, Tianjin, P.R. China."), [Zhenyi Ma](https://pubmed.ncbi.nlm.nih.gov/?term=Ma+Z&cauthor_id=42674816)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#short-view-affiliation-1 "Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China."), [Zhe Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+Z&cauthor_id=42674816)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42674816/#short-view-affiliation-6 "Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China; zheliu@hznu.edu.cn.") ### Affiliations * 1 Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China. * 2 School of Basic Medical Sciences, Central South University, Changsha, P.R. China. * 3 Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, P.R. China. * 4 Tianjin Medical University General Hospital, Tianjin, P.R. China. * 5 Department of Pathology, Tianjin Medical University, Tianjin, P.R. China. * 6 Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, P.R. China; zheliu@hznu.edu.cn. * PMID: **42674816** * DOI: [ 10.21873/cgp.20615 ](https://doi.org/10.21873/cgp.20615) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## 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. **Keywords:** Colorectal cancer; FN1; MIF; Th17 cells; cancer-associated fibroblasts; microsatellite-stable colorectal cancer; regulatory T cells; single-cell RNA sequencing; tumor microenvironment; whole-exome sequencing. Copyright © 2026 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. 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