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Cited by 358Cancer Immunotherapy and BiomarkersGenetic factors in colorectal cancerColorectal Cancer Treatments and Studies

Crosstalk Between the MSI Status and Tumor Microenvironment in Colorectal Cancer

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Lin, Anqi, Zhang, Jian, Luo, Peng·2020·Frontiers in Immunology
DOI 10.3389/fimmu.2020.02039PMC PMC7435056
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Abstract

Colorectal cancer (CRC) patients, especially those with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors, whose sensitivity to immune checkpoint inhibitors (ICIs) is significantly higher than that of patients with microsatellite-stable (MSS)/microsatellite instability-low (MSI-L) tumors, have derived clinical benefits from immunotherapy. Most studies have not systematically evaluated the immune characteristics and immune microenvironments of MSI-H and MSS/MSI-L CRCs. We analyzed the relationship between the MSI status and prognosis of ICI treatment in an immunotherapy cohort. We further used mutation data for the immunotherapy and The Cancer Genome Atlas (TCGA)-CRC [colon adenocarcinoma (COAD) + rectum adenocarcinoma (READ)] cohorts. For mRNA expression, mutation data analysis of the immune microenvironment and immunogenicity under different MSI statuses was performed. Compared with CRC patients with MSS/MSI-L tumors, those with MSI-H tumors significantly benefited from ICI treatment. MSI-H CRC had more immune cell infiltration, higher expression of immune-related genes, and higher immunogenicity than MSS/MSI-L CRC. The MANTIS score, which is used to predict the MSI status, was positively correlated with immune cells, immune-related genes, and immunogenicity. In addition, subtype analysis showed that COAD and READ might have different immune microenvironments. MSI-H CRC may have an inflammatory tumor microenvironment and increased sensitivity to ICIs. Unlike those of MSI-H READ, the immune characteristics of MSI-H COAD may be consistent with those of MSI-H CRC.

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  • Tregs suppress the harmful inflammatory response and thus exhibit positive benefits in patients with several types of cancers, including colorectal cancer and head and neck tumors.

    “Tregs suppress the harmful inflammatory response and thus exhibit positive benefits in patients with several types of cancers, including colorectal cancer (CRC) and head and neck tumors (HNC) [16, 18–21].”

    From Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review (2024) · cites this paper as [19]

    The Discussion (page unavailable) describes Tregs in colorectal cancer as inhibiting cytotoxic T-cell responses and suppressing other immune cells, not as providing a patient benefit by curbing harmful inflammation. The Results section, “Association of MSI-H With an Inflamed TME” (page unavailable), associates the inflammatory tumor environment with fewer Tregs. The paper does not address head and neck tumors in this context. (LLM, conf=0.87)

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Authors
Lin, A., Zhang, J., & Luo, P.
Affiliations
Zhujiang Hospital (CN)
Corresponding author
  • Zhang, Jian
  • Luo, Peng
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2020-08-12
Volume
11
Pages
2039-2039
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2020.02039
PMC
PMC7435056
OpenAlex
W3048754226
Cited by
358
References
49
Citations by year
2026: 28 · 2025: 55 · 2024: 81 · 2023: 72 · 2022: 87 · 2021: 34 · 2020: 1
FWCI
17.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Sun Yat-sen University
  • Universidade de Macau
  • Sun Yat-sen University Cancer Center
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords
colorectal cancer, microsatellite instability-high, microsatellite stable, tumor immune microenvironment, immune checkpoint inhibitors, immunotherapy response, immune cell infiltration, immune-related genes, immunogenicity, colon adenocarcinoma, rectal adenocarcinoma
MeSH terms
Immune Checkpoint Inhibitors, Disease Susceptibility, DNA Damage, Female, Humans, Male, Mutation, Prognosis, Colorectal Neoplasms, Signal Transduction, Treatment Outcome, Computational Biology, Disease Management, Gene Expression Profiling, Microsatellite Instability, Immunomodulation, Molecular Targeted Therapy, Tumor Microenvironment, Transcriptome

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