Open AccessIncreased IL-17 production correlates with immunosuppression involving myeloid-derived suppressor cells and nutritional impairment in patients with various gastrointestinal cancers
Author(s) -
Takashi Yazawa,
Masahiko Shibata,
Kenji Gonda,
Takeshi Machida,
Satoshi Suzuki,
Akira Kenjo,
Izumi Nakamura,
Takao Tsuchiya,
Yoshihisa Koyama,
Kenichi Sakurai,
Tatsuo Shimura,
Ryouichi Tomita,
Hitoshi Ohto,
Mitsukazu Gotoh,
Seiichi Takenoshita
Publication year - 2013
Publication title -
molecular and clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.442
H-Index - 7
eISSN - 2049-9469
pISSN - 2049-9450
DOI - 10.3892/mco.2013.134
Subject(s) - immunology , gastrointestinal cancer , immune system , inflammation , cancer , medicine , proinflammatory cytokine , cytokine , immunosuppression , myeloid , rheumatoid arthritis , lymphocyte , colorectal cancer
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.