title: Enhanced expression of PD-L1 in oral squamous cell carcinoma-derived CD11b(+)Gr-1(+) cells and its contribution to immunosuppressive activity.
abstract: Cancer is often associated with dysregulation of both the humoral and cellular immune response, which in some instances is believed to result from changes in immune cell populations. For example, immunosuppressive CD11b(+)Gr-1(+) myeloid-derived suppressor cells have been shown to proliferate in the tumor microenvironment and surrounding tissues, highlighting the relationship between tumor growth and impairment of the immune response. However, the role of myeloid-derived suppressor cells in cancer progression has not been fully characterized because these cells are heterogeneous with properties influenced by the type and location of the tumor. Here, we show that CD11b(+)Gr-1(+) cells are elevated in the peripheral blood, spleen, and tumor of mice with oral squamous cell carcinoma. The phenotype and function of these cells varied depending on the tissue of origin. In particular, CD11b(+)Gr-1(+) cells in tumors expressed PD-L1 more abundantly than those in other tissues. Accordingly, CD11b(+)Gr-1(+) cells from tumors, but not from the spleen, suppressed T cell proliferation in vitro. The results suggest that tumor-derived or immune factors result in the accumulation of phenotypically and functionally diverse populations of CD11b(+)Gr-1(+) cells in mice with oral squamous cell carcinoma. The data also indicate that PD-L1 expression in CD11b(+)Gr-1(+) cells contributes to immune suppression, implying that targeting both myeloid-derived suppressor cells and PD-L1 would be an effective immunotherapeutic strategy against oral cancer.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fuse
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Tomihara
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Heshiki
authors.affiliation: Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University, Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata City, Niigata 951-8514, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Akyu-Takei
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Hidetake
authors.initials: H
authors.lastname: Tachinami
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Furukawa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sakurai
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Moniruzzaman
authors.initials: M
authors.lastname: Rouwan
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism*; D018845:CD11 Antigens / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D007108:Immune Tolerance; D051379:Mice; D008809:Mice, Inbred C3H; D009062:Mouth Neoplasms / Q000276:immunology / Q000378:metabolism*; D022423:Myeloid Cells / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; D018845:CD11 Antigens; C498919:Cd274 protein, mouse
keywords: CD11b(+)Gr-1(+) cells; Immunosuppressive activity; Myeloid-derived suppressor cells; Oral cancer; PD-L1; Tumor-bearing mouse