Altered immunity to microbiota, B cell activation and depleted γδ/resident memory T cells in colorectal cancer

Noble, Alistair, Pring, Edward T., Durant, Lydia, Man, Ripple, Dilke, Stella M., Hoyles, Lesley, James, Steve A., Carding, Simon R., Jenkins, John T. and Knight, Stella C. (2022) Altered immunity to microbiota, B cell activation and depleted γδ/resident memory T cells in colorectal cancer. Cancer Immunology, Immunotherapy. ISSN 0340-7004

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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.

Item Type: Article
Additional Information: Funding Information: We acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); this research was funded by the Quadram Institute BBSRC Institute Strategic Programme Gut Microbes and Health BB/R012490/1 and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10356. Funding for A.N. and SCK was from London North West University Healthcare NHS Trust R&D.
Uncontrolled Keywords: b cell,colorectal cancer,gamma delta t cell,microbiota,resident memory t cell,oncology,cancer research,immunology and allergy,immunology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2730
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 31 Mar 2022 13:30
Last Modified: 06 May 2022 03:54
URI: https://ueaeprints.uea.ac.uk/id/eprint/84401
DOI: 10.1007/s00262-021-03135-8

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