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

Authors

Kenji Gonda

Kenji Gonda

Fukushima Medical University, Fukushima, Japan

Kenji Gonda, Masahiko Shibata, Daisuke Ujiie, Mai Ashizawa, Tomohiro Kikuchi, Hirokazu Okayama, Shoutarou Fujita, Wataru Sakamoto, Takahiro Nakajima, Hisahito Endo, Motonobu Saito, Tomoyuki Monma, Zenichiro Saze, Shinji Ohki, Koji Kono, Seiichi Takenoshita

Organizations

Fukushima Medical University, Fukushima, Japan

Research Funding

Other

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.

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Abstract Details

Meeting

2018 ASCO-SITC Clinical Immuno-Oncology Symposium

Session Type

Poster Session

Session Title

Poster Session B

Track

Developmental Therapeutics,Genitourinary Cancer,Head and Neck Cancer,Lung Cancer,Melanoma/Skin Cancers,Gastrointestinal Cancer,Breast and Gynecologic Cancers,Combination Studies,Implications for Patients and Society,Miscellaneous Cancers,Oncolytic Viruses,Hematologic Malignancies

Sub Track

Biomarkers and Inflammatory Signatures

Citation

J Clin Oncol 36, 2018 (suppl 5S; abstr 83)

DOI

10.1200/JCO.2018.36.5_suppl.83

Abstract #

83

Poster Bd #

E1

Abstract Disclosures

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