title: Invariant NKT cells are resistant to circulating CD15+ myeloid-derived suppressor cells in patients with head and neck cancer.
abstract: Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature and progenitor myeloid cells with an immunosuppressive role in various types of cancer, including head and neck squamous cell carcinoma (HNSCC). However, the effect on the host immune system, especially on invariant NKT (iNKT) cells with potent anti-tumor activity, remains unclear. In this study, we investigated the effects of circulating MDSC subsets on the peripheral lymphocytes of patients with head and neck tumors. A significant accumulation of CD15+ granulocytic MDSC (G-MDSC) and CD14+ monocytic MDSC (M-MDSC) was demonstrated in HNSCC patients. The percentage of G-MDSC showed an inverse correlation with the percentage of T cells in the peripheral blood. The increased G-MDSC was significantly associated with advanced clinical stage and poor prognosis of HNSCC patients. The proliferation and viability of T cells were suppressed by CD15+ cells, and the suppression was reversed by adding the hydrogen peroxide scavenger catalase. However, iNKT cell activation upon α-galactosylceramide (αGalCer) stimulation was not affected by the presence or absence of CD15+ G-MDSC. These results indicate that increased G-MDSC negatively affects peripheral T cell immunity, but not iNKT cells, in HNSCC patients, and that T cells are more sensitive to hydrogen peroxide produced by G-MDSC than iNKT cells. Cancer immunotherapy designed to enhance the antitumor activity of iNKT cells by stimulation with αGalCer may remain effective in the presence of G-MDSC.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Horinaka
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Sakurai
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Ihara
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Makita
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kunii
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000628:therapy; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005647:Fucosyltransferases / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000628:therapy; D006801:Humans; D016219:Immunotherapy, Adoptive; D016256:Lewis X Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000502:physiology*; D055611:Natural Killer T-Cells / Q000276:immunology*
chemical_list: D016256:Lewis X Antigen; C066693:FUT4 protein, human; D005647:Fucosyltransferases
keywords: Head and neck cancer; hydrogen peroxide; immune suppression; invariant NKT cell; squamous cell carcinoma