43 - Freie Mitteilung
16. Mai 2019, 08:30 - 10:00, Szenario 1, 5. OG
Interleukin-22 producing T cells promote neutrophil recruitment and better clinical outcome in human colorectal cancer
N. Tosti1, E. Cremonesi1, V. Governa1, V. Kancherla1, M. Coto1, F. Amicarella1, B. Weixler2, S. Däster1, G. Sconocchia3, G. C. Spagnoli1, 3, L. Tornillo1, L. M. Terracciano1, S. Eppenberger-Castori1, C. Ng1, S. Piscuoglio1, M. von Flüe1, G. Iezzi1, 4, R. A. Droeser1, Presenter: E. Cremonesi1 (1Basel, 2Berlin/DE, 3Rome/IT, 4Lugano)
T cell infiltration has been recognized to significantly impact clinical outcome in human colorectal cancer (CRC). Interleukin 22 (IL-22), a cytokine secreted by IL-17-producing CD4+ T cells (Th17) is known to play a crucial role in inflammatory bowel disease and has been shown to have protumorigenic activity in mouse tumor models. However, its role in human CRC is still unclear. As consequence, we evaluated the prognostic and functional impact of IL-22 producing cells in human CRC in this follow-up study.
In order to evaluate IL-22 expression in CRC, immunohistochemistry was performed on a well-characterized TMA including 425 cases of Primary CRC. Moreover, phenotypic characterization of IL-22 positive cells was assessed by flow cytometry of single cell suspensions. Next, in vitro experiments were done to further elucidate the effects of IL-22 on CRC cells.
IL-22 positive cells were detected both within tumor cells and tumor infiltrating immune cells. Whereas, IL-22 expression by tumor cells did not affect prognosis, densities of IL-22 positive immune cells were found to be significantly associated with early T stage and MMR-deficient microsatellite stability. Importantly, IL-22 expression by CRC infiltrating immune cells was predictive of improved overall survival independent of known prognostic factors such as T stage, N stage, tumor grade, vascular invasion, tumor border configuration and MMR status. Phenotypic characterization of IL-22 positive cells revealed that they consist mainly of polyfunctional CD4+ and CD8+ T cells, also producing IL-17 and IFN-g. Moreover, in vitro experiments showed a new role of IL-22 in stimulating CRC cells to release chemokines promoting neutrophils recruitment.
In conclusion, our data suggest that by stimulating production of neutrophil recruiting chemokines in tumor cells, IL-22-producing T cells might favor CRC infiltration by neutrophils, thus contributing to a more favorable clinical outcome.