title: Increased IL-17 production correlates with immunosuppression involving myeloid-derived suppressor cells and nutritional impairment in patients with various gastrointestinal cancers.
abstract: Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cell mechanisms mediating this relationship have not been elucidated. Th17 cells, which produce the proinflammatory cytokine interleukin 17 (IL-17), have been recognized as one of the key factors in the regulation of inflammatory bowel disease and rheumatoid arthritis. This study demonstrated that, in patients with various types of gastrointestinal cancer, IL-17 production was correlated with myeloid-derived suppressor cell (MDSC) levels and with markers for nutritional impairment, immune suppression and chronic inflammation. IL-17 was significantly higher in patients with various types of gastrointestinal cancer compared to normal volunteers. In addition, IL-17 levels were significantly correlated with neutrophil counts and the neutrophil/lymphocyte ratio (NLR) and significantly inversely correlated with cell-mediated immune response indicators [lymphocyte phytohemagglutinin (PHA)-blastogenesis and IL-12 induction] and patient nutritional status (prealbumin levels). Circulating MDSC levels were significantly correlated with IL-17 production. These results suggest that, in human gastrointestinal cancers, chronic inflammation involving IL-17 may be an important mechanism contributing to disease progression through enhancement of immune suppression or cachexia. Controlling the activation of Th17 cells may prove to be a valuable strategy for the treatment of gastrointestinal cancer patients.
authors.affiliation: Departments of Organ Regulatory Surgery, Fukushima 960-1295;
authors.forename: Takashi
authors.initials: T
authors.lastname: Yazawa
authors.affiliation: Departments of Organ Regulatory Surgery, Fukushima 960-1295; ; Tumor and Host Bioscience, Fukushima 960-1295;
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibata
authors.affiliation: Departments of Organ Regulatory Surgery, Fukushima 960-1295; ; Blood Transfusion and Transplantation Immunology, Fukushima 960-1295;
authors.forename: Kenji
authors.initials: K
authors.lastname: Gonda
authors.affiliation: Immunology, Fukushima 960-1295;
authors.forename: Takeshi
authors.initials: T
authors.lastname: Machida
authors.affiliation: Departments of Organ Regulatory Surgery, Fukushima 960-1295;
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Regenerative Surgery, Fukushima 960-1295;
authors.forename: Akira
authors.initials: A
authors.lastname: Kenjo
authors.affiliation: Departments of Organ Regulatory Surgery, Fukushima 960-1295;
authors.forename: Izumi
authors.initials: I
authors.lastname: Nakamura
authors.affiliation: Regenerative Surgery, Fukushima 960-1295;
authors.forename: Takao
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Departments of Organ Regulatory Surgery, Fukushima 960-1295;
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Koyama
authors.affiliation: Department of Surgery, Nihon University School of Medicine, Itabashi, Tokyo 173-8610;
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sakurai
authors.affiliation: Departments of Organ Regulatory Surgery, Fukushima 960-1295; ; Tumor and Host Bioscience, Fukushima 960-1295;
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shimura
authors.affiliation: Department of Surgery, Nippon Dental University, Chiyoda, Tokyo 102-8158, Japan.
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Tomita
authors.affiliation: Blood Transfusion and Transplantation Immunology, Fukushima 960-1295;
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohto
authors.affiliation: Regenerative Surgery, Fukushima 960-1295;
authors.forename: Mitsukazu
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Departments of Organ Regulatory Surgery, Fukushima 960-1295;
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
keywords: cachexia; gastrointestinal cancer; immune suppression; myeloid-derived suppressor cells; nutritional impairment