Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer

Amicarella, Francesca and Muraro, Manuele Giuseppe and Hirt, Christian and Cremonesi, Eleonora and Padovan, Elisabetta and Mele, Valentina and Governa, Valeria and Han, Junyi and Huber, Xaver and Droeser, Raoul Andre and Zuber, Michel and Adamina, Marco and Bolli, Martin and Rosso, Raffaele and Lugli, Alessandro and Zlobec, Inti and Terracciano, Luigi and Tornillo, Luigi and Zajac, Paul and Eppenberger-Castori, Serenella and Trapani, Francesca and Oertli, Daniel and Iezzi, Giandomenica. (2017) Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer. Gut, 66 (4). pp. 692-704.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/61932/

Downloads: Statistics Overview


BACKGROUND: The immune contexture predicts prognosis in human colorectal cancer (CRC). Whereas tumour-infiltrating CD8+ T cells and myeloid CD16+ myeloperoxidase (MPO)+ cells are associated with favourable clinical outcome, interleukin (IL)-17-producing cells have been reported to correlate with severe prognosis. However, their phenotypes and functions continue to be debated. OBJECTIVE: To investigate clinical relevance, phenotypes and functional features of CRC-infiltrating, IL-17-producing cells. METHODS: IL-17 staining was performed by immunohistochemistry on a tissue microarray including 1148 CRCs. Phenotypes of IL-17-producing cells were evaluated by flow cytometry on cell suspensions obtained by enzymatic digestion of clinical specimens. Functions of CRC-isolated, IL-17-producing cells were assessed by in vitro and in vivo experiments. RESULTS: IL-17+ infiltrates were not themselves predictive of an unfavourable clinical outcome, but correlated with infiltration by CD8+ T cells and CD16+ MPO+ neutrophils. Ex vivo analysis showed that tumour-infiltrating IL-17+ cells mostly consist of CD4+ T helper 17 (Th17) cells with multifaceted properties. Indeed, owing to IL-17 secretion, CRC-derived Th17 triggered the release of protumorigenic factors by tumour and tumour-associated stroma. However, on the other hand, they favoured recruitment of beneficial neutrophils through IL-8 secretion and, most importantly, they drove highly cytotoxic CCR5+CCR6+CD8+ T cells into tumour tissue, through CCL5 and CCL20 release. Consistent with these findings, the presence of intraepithelial, but not of stromal Th17 cells, positively correlated with improved survival. CONCLUSIONS: Our study shows the dual role played by tumour-infiltrating Th17 in CRC, thus advising caution when developing new IL-17/Th17 targeted treatments.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cancer Immunotherapy (Iezzi)
UniBasel Contributors:Iezzi, Giandomenica
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:British Medical Association
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:23 Apr 2020 14:28
Deposited On:23 Apr 2020 14:28

Repository Staff Only: item control page