Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis
Open accessAbstract
Colorectal cancers with high-frequency microsatellite instability show peculiar clinicopathological features and a favorable clinical outcome. We investigated whether the improved prognosis for these cancers is related to the content of activated cytotoxic intraepithelial T lymphocytes. Microsatellite instability and the amount of activated cytotoxic lymphocytes were analyzed according to clinicopathological features, survival, and disease recurrence in 109 right-sided colon carcinomas from 245 consecutive patients with stage II/III colon cancer that underwent radical surgery. High-frequency microsatellite instability was found in 43% of stage II/III proximal colon cancers and was associated with significantly higher numbers of activated cytotoxic lymphocytes. High-frequency microsatellite instability, as well as the content of intratumoral-activated cytotoxic T lymphocytes correlated with improved overall and disease-free survival, particularly in patients with stage III tumors. Multivariate analysis revealed that patients with both features had a risk of death and relapse markedly lower than that associated with microsatellite status or intratumoral cytotoxic lymphocytes separately. The presence of local cytotoxic immune responses is probably the major determinant of the good clinical course of patients with microsatellite unstable colon cancer. Furthermore, high-frequency microsatellite instability coupled with a high content of intratumoral cytotoxic lymphocytes may identify a subset of colon cancer patients with a favorable clinical outcome, particularly in stage III disease.
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In dMMR/MSI-H colorectal cancers, heightened immunogenicity leads to a significantly increased number of tumor-infiltrating CD8+ T lymphocytes and a good prognosis.
“In the case of dMMR/MSI-H CRCs, there is heightened immunogenicity, leading to a significantly increased number of tumor-infiltrating CD8+ T lymphocytes (TILs) and a good prognosis [68,69].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [68]
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- Authors
- Guidoboni, M., Gafà, R., Viel, A., Doglioni, C., Russo, A., Santini, A., Del Tin, L., Macrì, E., Lanza, G., Boiocchi, M., & Dolcetti, R.
- Affiliations
- University of Ferrara (IT)
- Centro di Riferimento Oncologico (IT)
- Istituto per lo Studio e la Prevenzione Oncologica (IT)
- Arcispedale Sant'Anna (IT)
- Corresponding author
- Boiocchi, Mauro
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2001-07
- Volume
- 159
- Issue
- 1
- Pages
- 297-304
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1850401
- OpenAlex
- W2006924771
- Cited by
- 322
- References
- 33
- Citations by year
- 2025: 9 · 2024: 11 · 2023: 11 · 2022: 9 · 2021: 13 · 2020: 12 · 2019: 20 · 2018: 9 · 2017: 12 · 2016: 13 · 2015: 15 · 2014: 13 · 2013: 17 · 2012: 7
- FWCI
- 10.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- microsatellite instability, colon cancer, cytotoxic T lymphocytes, intratumoral lymphocytes, antitumor immunity, prognosis, disease-free survival, overall survival, recurrence
- MeSH terms
- Aged, Colonic Neoplasms, Female, Humans, Intestinal Mucosa, Male, Middle Aged, Neoplasm Staging, Phenotype, Prognosis, T-Lymphocytes, Cytotoxic, Survival Analysis, Microsatellite Repeats
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