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Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer: possible implications for immunotherapy
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.ORCID iD: 0000-0002-1901-8011
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.ORCID iD: 0000-0002-4688-8952
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
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2024 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 130Article in journal (Refereed) Published
Abstract [en]

Background: The immune response has important clinical value in colorectal cancer (CRC) in both prognosis and response to immunotherapy. This study aims to explore tumour immune cell infiltration in relation to clinically well-established molecular markers of CRC.

Methods: Multiplex immunohistochemistry and multispectral imaging was used to evaluate tumour infiltration of cytotoxic T cells (CD8+), Th1 cells (T-bet+), T regulatory cells (FoxP3+), B cells (CD20+), and macrophages (CD68+) in a cohort of 257 CRC patients.

Results: We found the expected association between higher immune-cell infiltration and microsatellite instability. Also, whereas BRAF-mutated tumours displayed increased immune-cell infiltration compared to BRAF wild-type tumours, the opposite was seen for KRAS-mutated tumours, differences that were most prominent for cytotoxic T cells and Th1 cells. The opposing relationships of BRAF and KRAS mutations with tumour infiltration of cytotoxic T cells was validated in an independent cohort of 608 CRC patients. A positive prognostic importance of cytotoxic T cells was found in wild-type as well as KRAS and BRAF-mutated CRCs in both cohorts.

Conclusion: A combined evaluation of MSI status, KRAS and BRAF mutational status, and immune infiltration (cytotoxic T cells) may provide important insights to prognosis and response to immunotherapy in CRC.

Place, publisher, year, edition, pages
Springer Nature, 2024. Vol. 130
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-217735DOI: 10.1038/s41416-023-02483-9ISI: 001124195700002PubMedID: 38040818Scopus ID: 2-s2.0-85178212553OAI: oai:DiVA.org:umu-217735DiVA, id: diva2:1818922
Funder
Sjöberg FoundationSwedish Cancer SocietyVästerbotten County CouncilAvailable from: 2023-12-12 Created: 2023-12-12 Last updated: 2024-05-07Bibliographically approved

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Edin, SofiaGylling, BjörnLi, XingruStenberg, ÅsaLöfgren Burström, AnnaZingmark, Carlvan Guelpen, BethanyLjuslinder, IngridLing, AgnesPalmqvist, Richard

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Edin, SofiaGylling, BjörnLi, XingruStenberg, ÅsaLöfgren Burström, AnnaZingmark, Carlvan Guelpen, BethanyLjuslinder, IngridLing, AgnesPalmqvist, Richard
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PathologyDepartment of Radiation SciencesWallenberg Centre for Molecular Medicine at Umeå University (WCMM)
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British Journal of Cancer
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