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Gut. 2017 Apr;66(4):692-704. doi: 10.1136/gutjnl-2015-310016. Epub 2015 Dec 30.

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

Author information

1
Department of Biomedicine, Institute of Surgical Research, University of Basel, Basel, Switzerland.
2
Institute of Pathology, University of Basel, Basel, Switzerland.
3
Department of General Surgery, Shanghai East Hospital, Tongji University, Shanghai, China.
4
Department of General Surgery, University Hospital Basel, Basel, Switzerland.
5
Department of Visceral Surgery, Kantonsspital Olten, Olten, Switzerland.
6
Department of Visceral Surgery, Kantonsspital St Gallen, St. Gallen, Switzerland.
7
Department of Visceral Surgery, St Claraspital, Basel, Switzerland.
8
Department of Visceral Surgery, Ospedale Civico Lugano, Lugano, Switzerland.
9
Institute of Pathology, University of Bern, Bern, Switzerland.

Abstract

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.

KEYWORDS:

CANCER IMMUNOBIOLOGY; COLORECTAL CANCER; IMMUNE RESPONSE; INFLAMMATORY MEDIATORS; T LYMPHOCYTES

PMID:
26719303
PMCID:
PMC5529969
DOI:
10.1136/gutjnl-2015-310016
[Indexed for MEDLINE]
Free PMC Article

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