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

Authors
  • Noble, Alistair1, 2
  • Pring, Edward T2, 3
  • Durant, Lydia2
  • Man, Ripple3
  • Dilke, Stella M2, 3
  • Hoyles, Lesley4
  • James, Steve A1
  • Carding, Simon R1, 5
  • Jenkins, John T3
  • Knight, Stella C6, 7
  • 1 Gut Microbes and Health Program, Quadram Institute Bioscience, Norwich, UK.
  • 2 Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, Harrow, UK.
  • 3 St. Mark's Hospital, London North West University Healthcare NHS Trust, Harrow, UK.
  • 4 Department of Biosciences, Nottingham Trent University, Nottingham, UK.
  • 5 Norwich Medical School, University of East Anglia, Norwich, UK.
  • 6 Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, Harrow, UK. [email protected]
  • 7 St. Mark's Hospital, London North West University Healthcare NHS Trust, Harrow, UK. [email protected]
Type
Published Article
Journal
Cancer Immunology Immunotherapy
Publisher
Springer-Verlag
Publication Date
Nov 01, 2022
Volume
71
Issue
11
Pages
2619–2629
Identifiers
DOI: 10.1007/s00262-021-03135-8
PMID: 35316367
Source
Medline
Keywords
Language
English
License
Unknown

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. © 2022. Crown.

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