title: Immunosuppressive activity of CD14+ HLA-DR- cells in squamous cell carcinoma of the head and neck.
abstract: Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population and have the potential to suppress immune responses via diverse mechanisms. In recent studies, a new subset of MDSC was identified by the markers CD14(+) and HLA-DR(-) in the peripheral blood from cancer patients. In this study, we investigated the proportions and characteristics of CD14(+) HLA-DR(-) cells in patients with squamous cell carcinoma of the head and neck (SCCHN). As expected, the percentage of CD14(+) HLA-DR(-) cells was significantly elevated in patients relative to healthy donors and the sorted CD14(+) HLA-DR(-) cells were able to suppress effectively both the proliferation and IFN-γ production of anti-CD3/anti-CD28 stimulated T cells, suggesting that CD14(+) HLA-DR(-) cells in patients with SCCHN contribute to the immune suppressive status. Furthermore, CD14(+) HLA-DR(-) cells revealed a higher level of CD86 and PD-L1 expression and transforming growth factor (TGF)-β production than CD14(+) HLA-DR(+) cells. Addition of anti-CD86 mAb, anti-PD-L1 mAb and anti-TGF-β mAb partially restored T-cell proliferation and IFN-γ production, respectively, indicating that the suppressive effects of CD14(+) HLA-DR(-) cells appear to be mediated by various molecules, including coinhibitory molecules and cytokines. Our data suggest that CD14(+) HLA-DR(-) cells act as potent immunosuppressive cells and particularly contribute to tumor escape from the host immune system in patients with SCCHN.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan. tikamatu@gunma-u.ac.jp
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chikamatsu
authors.forename: Koichi
authors.initials: K
authors.lastname: Sakakura
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyoda
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Masuyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D051940:B7-2 Antigen / Q000032:analysis / Q000276:immunology; D060890:B7-H1 Antigen / Q000032:analysis / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D006684:HLA-DR Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma