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

Alistair Noble, Edward T. Pring, Lydia Durant, Ripple Man, Stella M. Dilke, Lesley Hoyles, Steve A. James, Simon R. Carding, John T. Jenkins, Stella C. Knight

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)2619–2629
Number of pages11
JournalCancer Immunology, Immunotherapy
Issue number11
Early online date22 Mar 2022
Publication statusPublished - Nov 2022


  • B cell
  • Colorectal cancer
  • Gamma delta T cell
  • Microbiota
  • Resident memory T cell

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