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10.1136/gutjnl-2015-310016

http://scihub22266oqcxt.onion/10.1136/gutjnl-2015-310016
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C5529969!5529969!26719303
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suck abstract from ncbi


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pmid26719303      Gut 2017 ; 66 (4): 692-704
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  • Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer #MMPMID26719303
  • Amicarella F; Muraro MG; Hirt C; Cremonesi E; Padovan E; Mele V; Governa V; Han J; Huber X; Droeser RA; Zuber M; Adamina M; Bolli M; Rosso R; Lugli A; Zlobec I; Terracciano L; Tornillo L; Zajac P; Eppenberger-Castori S; Trapani F; Oertli D; Iezzi G
  • Gut 2017[Apr]; 66 (4): 692-704 PMID26719303show ga
  • 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.
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