dc.contributor.author | Porter, RJ | |
dc.contributor.author | Murray, GI | |
dc.contributor.author | Alnabulsi, A | |
dc.contributor.author | Humphries, MP | |
dc.contributor.author | James, JA | |
dc.contributor.author | Salto-Tellez, M | |
dc.contributor.author | Craig, SG | |
dc.contributor.author | Wang, JM | |
dc.contributor.author | Yoshimura, T | |
dc.contributor.author | McLean, MH | |
dc.date.accessioned | 2021-08-05T09:48:55Z | |
dc.date.available | 2021-08-05T09:48:55Z | |
dc.date.issued | 2021-05-14 | |
dc.identifier.citation | The journal of pathology. Clinical research, 2021 | |
dc.identifier.issn | 2056-4538 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4723 | |
dc.identifier.eissn | 2056-4538 | |
dc.identifier.doi | 10.1002/cjp2.222 | |
dc.description.abstract | Colorectal 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+ , CD4+ , and CD8+ 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+ 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.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Colonic epithelial cathelicidin (LL-37) expression intensity is associated with progression of colorectal cancer and presence of CD8+ T cell infiltrate. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-04-14 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1002/cjp2.222 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-05-14 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | The journal of pathology. Clinical research | |
pubs.notes | Not 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-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Integrated Pathology | |
icr.researchteam | Integrated Pathology | |
dc.contributor.icrauthor | Salto-Tellez, Manuel | |