Abstract 1285: Production of interleukin-17 is increased in patients with gastrointestinal cancer and correlates with immune suppression involving MDSC, nutritional impairment, and poor prognosis

Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cellular mechanisms mediating this relationship remain unclear. Th17 cells, which produce the proinflammatory cytokine IL-17, have been recognized as one of the key factors in regulation of inflammatory bowel disease and rheumatoid arthritis. IL-17 also has recently been reported to play an important role in induction of MDSC (myeloid-derived suppressor cells). This study demonstrated that, in patients with gastric and colorectal cancers, IL-17 production was correlated with MDSC level and with markers for nutritional impairment, immune suppression and chronic inflammation. IL-17 was significantly higher in patients with gastrointestinal cancer than in normal volunteers. In addition, IL-17 levels were significantly correlated with neutrophil counts and the neutrophil/lymphocyte ratio, and significantly inversely correlated with cell mediated immune response indicators (lymphocyte PHA-blastogenesis and IL-12 induction) and patients’ nutritional status (prealbumin levels). These patients were separated into two groups with the production of IL-17 and the overall survival of the patients with higher production of IL-17 was significantly worse than those with lower production of it. These results suggest that, in human gastrointestinal cancers, chronic inflammation involving IL-17 may be an important mechanism for disease progression through enhancement of induction of MDSC resulting immune suppression, or cachexia. The production of IL-17 was also demonstrated as one of the effective prognostic indicators in these patients. Controlling activation of Th17 cells may prove to be a valuable strategy for treatment of patients with gastrointestinal cancer. Further studies are warranted to explore this possibility. Citation Format: Masahiko Shibata, Kenji Gonda, Takahiro Nakajima, Shinji Ohki, Izumi Nakamura, Tatsuo Shimura, Koji Kono, Seiichi Takenoshita. Production of interleukin-17 is increased in patients with gastrointestinal cancer and correlates with immune suppression involving MDSC, nutritional impairment, and poor prognosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1285. doi:10.1158/1538-7445.AM2015-1285