Altered immunity to microbiota, B cell activation and depleted γδ/resident memory T cells in colorectal cancer
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Abstract
The role of microbiota:immune system dysregulation in the etiology of colorectal cancer (CRC) is poorly understood. CRC develops in gut epithelium, accompanied by low level inflammatory signaling, intestinal microbial dysbiosis and immune dysfunction. We examined populations of intraepithelial lymphocytes in non-affected colonic mucosa of CRC and healthy donors and circulating immune memory to commensal bacterial species and yeasts. γδ T cells and resident memory T cells, populations with a regulatory CD39-expressing phenotype, were found at lower frequencies in the colonic tissue of CRC donors compared to healthy controls. Patterns of T cell proliferative responses to a panel of commensal bacteria were distinct in CRC, while B cell memory responses to several bacteria/yeast were significantly increased, accompanied by increased proportions of effector memory B cells, transitional B cells and plasmablasts in blood. IgA responses to mucosal microbes were unchanged. Our data describe a novel immune signature with similarities to and differences from that of inflammatory bowel disease. They implicate B cell dysregulation as a potential contributor to parainflammation and identify pathways of weakened barrier function and tumor surveillance in CRC-susceptible individuals.
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B cell proliferative responses to several commensals, mainly Bacteroides ovatus, Hafnia spp., V. atypica and C. albicans, were higher in CRC patients than in healthy volunteers.
“Moreover, B cell proliferative responses to several commensals, mostly Bacteroides ovatus, Hafnia spp., V. atypica and C. albicans, were increased in patients with CRC compared with healthy volunteers118.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [118]
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Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy
Thomas, A. M., Fidelle, M., Routy, B., Kroemer, G., Wargo, J. A., Segata, N., & Zitvogel, L. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00785-8 · Cited by 141 · see citing works
- Authors
- Noble, A., Pring, E. T., Durant, L., Man, R., Dilke, S. M., Hoyles, L., James, S. A., Carding, S. R., Jenkins, J. T., & Knight, S. C.
- Affiliations
- Quadram Institute (GB)
- London North West Healthcare NHS Trust (GB)
- Imperial College London (GB)
- Nottingham Trent University (GB)
- University of East Anglia (GB)
- Corresponding author
- Knight, Stella C.
- ORCID
- Venue
- Cancer Immunology, Immunotherapy
- Published
- 2022-03-22
- Volume
- 71
- Issue
- 11
- Pages
- 2619-2629
- ISSN
- 0340-7004 (ISSN-L)
- 1432-0851
- PMC
- PMC9519644
- OpenAlex
- W4220711426
- Cited by
- 34
- References
- 43
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 7 · 2023: 9 · 2022: 3
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cancer Immunology Immunotherapy (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (acceptedVersion)
- Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/R012490/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- colorectal cancer, gut microbiota, γδ T cells, tissue-resident memory T cells, intraepithelial lymphocytes, B cell activation, commensal bacteria, yeast, CD39, T cell proliferative response, transitional B cells, plasmablasts, IgA, intestinal barrier function, tumor surveillance, parainflammation, inflammatory bowel disease
- MeSH terms
- Memory T Cells, Bacteria, Humans, Immunoglobulin A, Intestinal Mucosa, Colorectal Neoplasms, Microbiota, Dysbiosis
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