Show simple item record

dc.contributor.authorPorter, RJ
dc.contributor.authorMurray, GI
dc.contributor.authorAlnabulsi, A
dc.contributor.authorHumphries, MP
dc.contributor.authorJames, JA
dc.contributor.authorSalto-Tellez, M
dc.contributor.authorCraig, SG
dc.contributor.authorWang, JM
dc.contributor.authorYoshimura, T
dc.contributor.authorMcLean, MH
dc.date.accessioned2021-08-05T09:48:55Z
dc.date.available2021-08-05T09:48:55Z
dc.date.issued2021-05-14
dc.identifier.citationThe journal of pathology. Clinical research, 2021
dc.identifier.issn2056-4538
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4723
dc.identifier.eissn2056-4538
dc.identifier.eissn2056-4538en_US
dc.identifier.doi10.1002/cjp2.222
dc.identifier.doi10.1002/cjp2.222en_US
dc.description.abstractColorectal cancer (CRC) remains a leading cause of cancer mortality. Here, we define the colonic epithelial expression of cathelicidin (LL-37) in CRC. Cathelicidin exerts pleotropic effects including anti-microbial and immunoregulatory functions. Genetic knockout of cathelicidin led to increased size and number of colorectal tumours in the azoxymethane-induced murine model of CRC. We aimed to translate this to human disease. The expression of LL-37 in a large (n = 650) fully characterised cohort of treatment-naïve primary human colorectal tumours and 50 matched normal mucosa samples with associated clinical and pathological data (patient age, gender, tumour site, tumour stage [UICC], presence or absence of extra-mural vascular invasion, tumour differentiation, mismatch repair protein status, and survival to 18 years) was assessed by immunohistochemistry. The biological consequences of LL-37 expression on the epithelial barrier and immune cell phenotype were assessed using targeted quantitative PCR gene expression of epithelial permeability (CLDN2, CLDN4, OCLN, CDH1, and TJP1) and cytokine (IL-1β, IL-18, IL-33, IL-10, IL-22, and IL-27) genes in a human colon organoid model, and CD3<sup>+</sup> , CD4<sup>+</sup> , and CD8<sup>+</sup> lymphocyte phenotyping by immunohistochemistry, respectively. Our data reveal that loss of cathelicidin is associated with human CRC progression, with a switch in expression intensity an early feature of CRC. LL-37 expression intensity is associated with CD8<sup>+</sup> T cell infiltrate, influenced by tumour characteristics including mismatch repair protein status. There was no effect on epithelial barrier gene expression. These data offer novel insights into the contribution of LL-37 to the pathogenesis of CRC and as a therapeutic molecule.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleColonic epithelial cathelicidin (LL-37) expression intensity is associated with progression of colorectal cancer and presence of CD8<sup>+</sup> T cell infiltrate.
dc.typeJournal Article
dcterms.dateAccepted2021-04-14
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1002/cjp2.222
rioxxterms.licenseref.startdate2021-05-14
rioxxterms.licenseref.startdate2021-05-14en_US
dc.relation.isPartOfThe journal of pathology. Clinical research
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/ImmNet
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/ImmNet
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
pubs.publication-statusPublished
pubs.embargo.termsNot known
icr.researchteamIntegrated Pathology
icr.researchteamIntegrated Pathologyen_US
dc.contributor.icrauthorSalto-Tellez, Manuelen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/