Microsatellite Instability in Colorectal Cancers: Carcinogenesis, Neo-Antigens, Immuno-Resistance and Emerging Therapies

Randrian, Violaine; Evrard, Camille; Tougeron, David

doi:10.3390/cancers13123063

Cited by 65Genetic factors in colorectal cancerCancer Immunotherapy and BiomarkersColorectal Cancer Treatments and Studies

Microsatellite Instability in Colorectal Cancers: Carcinogenesis, Neo-Antigens, Immuno-Resistance and Emerging Therapies

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Randrian, Violaine, Evrard, Camille, Tougeron, David·2021·Cancers

DOI 10.3390/cancers13123063PMC PMC8235567

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Abstract

A defect in the DNA repair system through a deficient mismatch repair system (dMMR) leads to microsatellite instability (MSI). Microsatellites are located in both coding and non-coding sequences and dMMR/MSI tumors are associated with a high mutation burden. Some of these mutations occur in coding sequences and lead to the production of neo-antigens able to trigger an anti-tumoral immune response. This explains why non-metastatic MSI tumors are associated with high immune infiltrates and good prognosis. Metastatic MSI tumors result from tumor escape to the immune system and are associated with poor prognosis and chemoresistance. Consequently, immune checkpoint inhibitors (ICI) are highly effective and have recently been approved in dMMR/MSI metastatic colorectal cancers (mCRC). Nevertheless, some patients with dMMR/MSI mCRC have primary or secondary resistance to ICI. This review details carcinogenesis and the mechanisms through which MSI can activate the immune system. After which, we discuss mechanistic hypotheses in an attempt to explain primary and secondary resistances to ICI and emerging strategies being developed to overcome this phenomenon by targeting other immune checkpoints or through vaccination and modification of microbiota.

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MSI/dMMR could be a prognostic test in ICI-based immunotherapy to show how tumours respond to antibodies, particularly in cancers such as colorectal, gastric cancer and endometriosis.
“Currently, discovered that MSI/dMMR could be a prognostic test in ICI-based immunotherapy to show how tumours respond to antibodies, particularly in cancers such as colorectal, gastric cancer and endometriosis [114].”
From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [114]

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Immune Checkpoint Inhibitors in Cancer Therapy
Shiravand, Y., Khodadadi, F., Kashani, S. M. A., Hosseini-Fard, S. R., Hosseini, S., Sadeghirad, H., Ladwa, R., O’Byrne, K., & Kulasinghe, A. (2022) · Current Oncology · doi:10.3390/curroncol29050247 · Cited by 1,353 · see citing works
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Authors: Randrian, V., Evrard, C., & Tougeron, D.
Affiliations: Université de Poitiers (FR)
Centre Hospitalier Universitaire de Poitiers (FR)
Corresponding author: Randrian, Violaine
ORCID: Randrian, Violaine
Evrard, Camille
Tougeron, David
Venue: Cancers
Publisher: MDPI AG
Published: 2021-06-19
Volume: 13
Issue: 12
Pages: 3063
ISSN: 2072-6694 (ISSN-L)
DOI: 10.3390/cancers13123063
PMC: PMC8235567
OpenAlex: W3173665078
Cited by: 65
References: 113
Citations by year: 2026: 8 · 2025: 16 · 2024: 7 · 2023: 13 · 2022: 16 · 2021: 3 · 2013: 1
FWCI: 1.71
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Cancers (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
HAL (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords: microsatellite instability, colorectal cancer, mismatch repair deficiency, DNA repair deficiency, neoantigens, tumor immune infiltrate, immune checkpoint inhibitors, immune resistance, chemoresistance, metastatic colorectal cancer, tumor immunogenicity, cancer vaccination, gut microbiota

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Microsatellite Instability in Colorectal Cancers: Carcinogenesis, Neo-Antigens, Immuno-Resistance and Emerging Therapies

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