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Cited by 52Cancer Immunotherapy and BiomarkersGenetic factors in colorectal cancerColorectal Cancer Treatments and Studies

Unraveling resistance to immunotherapy in MSI-high colorectal cancer

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Heregger, Ronald, Huemer, Florian, Steiner, Markus, Gonzalez-Martinez, Alejandra, Greil, Richard, Weiss, Lukas·2023·Cancers
DOI 10.3390/cancers15205090PMC PMC10605634
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Abstract

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths. Incidences of early CRC cases are increasing annually in high-income countries, necessitating effective treatment strategies. Immune checkpoint inhibitors (ICIs) have shown significant clinical efficacy in various cancers, including CRC. However, their effectiveness in CRC is limited to patients with mismatch-repair-deficient (dMMR)/microsatellite instability high (MSI-H) disease, which accounts for about 15% of all localized CRC cases and only 3% to 5% of metastatic CRC cases. However, the varied response among patients, with some showing resistance or primary tumor progression, highlights the need for a deeper understanding of the underlying mechanisms. Elements involved in shaping the response to ICIs, such as tumor microenvironment, immune cells, genetic changes, and the influence of gut microbiota, are not fully understood thus far. This review aims to explore potential resistance or immune-evasion mechanisms to ICIs in dMMR/MSI-H CRC and the cell types involved, as well as possible pitfalls in the diagnosis of this particular subtype.

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  • 30-40% of MSI-H CRC patients show no response to immunotherapy, and around 20-25% develop resistance to this treatment.

    “However, 30–40% of MSI-H CRC patients show no response to immunotherapy, and around 20–25% develop resistance to this treatment [50].”

    From Inhibition of fatty acid synthase enhances therapeutic efficacy and delays acquired resistance to BRAF-targeted therapy in colorectal cancer (2026) · cites this paper as [50]

    The Introduction reports that about 30–40% of patients with metastatic dMMR/MSI-H colorectal cancer do not respond to immune checkpoint inhibitors. It also says about 20–25% are refractory to treatment, but does not say that this percentage develops resistance after treatment begins; the Simple Summary says only that some develop resistance. The citing sentence also omits the metastatic qualifier on the 30–40% figure. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Heregger, R., Huemer, F., Steiner, M., Gonzalez-Martinez, A., Greil, R., & Weiss, L.
Affiliations
  • Paracelsus Medical University (AT)
  • Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Center for Clinical Cancer and Immunology Trials (CCCIT), Paracelsus Medical University, 5020 Salzburg, Austria
Corresponding author
Weiss, Lukas
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2023-10-21
Volume
15
Issue
20
Pages
5090
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers15205090
PMC
PMC10605634
OpenAlex
W4387843564
Cited by
52
References
17
Citations by year
2026: 20 · 2025: 19 · 2024: 13
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
SCRI-LIMCR, the City of Salzburg, the Province of Salzburg, WISS 2025
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, immune checkpoint inhibitors, immunotherapy resistance, mismatch repair deficiency, tumor immune microenvironment, tumor-infiltrating immune cells, gut microbiota, immune evasion, metastatic colorectal cancer, diagnostic pitfalls

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