Correlation of IL-17 with immune suppression involving MDSC, malnutrition, and prognosis in patients with gastric and colorectal cancer.

Abstract

83 Background: Although a causal relationship linking inflammation and cancer immunity is more widely accepted today, precise cell mechanisms mediating this relationship have not been elucidated. IL-17, a pro-inflammatory cytokine primarily secreted by T helper (Th)17 cells, has previously been associated with inflammatory processes in autoimmune disease. The presence of IL-17 and Th17 cells has been confirmed in various invasive cancers and recently linked to immunosuppression in cancer patients. We investigated systemic inflammation, immune suppression, malnutrition, and prognosis associated with IL-17 in patients with gastric and colorectal cancer. Methods: We measured IL-17 in 106 patients, including 43 with gastric and 63 with colorectal cancer, Production of IL-17 stimulated by PHA was measured by ELISA. MDSC (myeloid-derived suppressor cells), which significantly contribute to immunosuppression, were measured by flow cytometry (CD11b+CD14-CD33+). Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were used as inflammatory markers. Production of IL-12 and the SI (stimulation index) of lymphocytes’ blastogenic response were used as markers of cell-mediated immune response. Results: Production of IL-17 increased in advanced stages of gastric and colorectal cancer. IL-17 positively correlated with levels of MDSC, serum concentrations of VEGF, NLR, and levels of CRP, and was inversely correlated with IL-12 production, SI, and nutritional markers including prealbumin and retinol binding protein. Patient cohorts were divided into two groups with IL-17 level (540 pg/ml) and OS (overall survival) of patients with stages III and IV gastric or colorectal cancer both significantly worse in patients with high production of IL-17 than in those with low IL-17, although the differences were not significant in patients at stages I and II. Conclusions: The present study suggests that IL-17 may reflect an inflammatory impact on the advancement and progression of cancer, and it may serve as useful marker of immune suppression involving MDSC, malnutrition, and poor prognosis in patients with gastric and colorectal cancer.