title: HPV16 E2 protein promotes innate immunity by modulating immunosuppressive status.
abstract: The balance between active immune responses against human papillomavirus (HPV) and HPV-induced immune escape regulates viral clearance and carcinogenesis. To understand the role of the early viral protein HPV16 E2 in host innate immune responses, the HPV16 E2-transfected murine squamous cell carcinoma cell line SCCVII (SCC/E2) was generated and anti-tumor responses in T-cell-depleted mice were evaluated. Tumor growth of SCC/E2 was markedly reduced. Cytotoxicity against the NK-sensitive targets YAC-1 and SCCVII was clearly enhanced in SCC/E2-inoculated mice. Despite the comparable ratio of NK cells, the proportion of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) was significantly decreased in SCC/E2-inoculated mice. The transcription of MDSC-related mediators such as inducible nitric oxide synthase, indoleamine 2,3-dioxygenase, and heme oxygenase-1 was significantly impaired in the SCC/E2-inoculated tumor tissues on day 3. Our results suggest that HPV16 E2 promotes anti-tumor innate effector function by modulating immunoregulatory events mediated by MDSCs and their mediators. This report describes a new role for HPV16 E2 as a local immunomodulator at infected sites.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Nuchsupha
authors.initials: N
authors.lastname: Sunthamala
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Chamsai
authors.initials: C
authors.lastname: Pientong
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Tatsukuni
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Bhingare
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. Electronic address: miyuki.mim@tmd.ac.jp.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Azuma
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: tipeka@kku.ac.th.
authors.forename: Tipaya
authors.initials: T
authors.lastname: Ekalaksananan
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D051547:Heme Oxygenase-1 / Q000276:immunology; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology*; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D014162:Transfection
chemical_list: D018925:Chemokines; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D051547:Heme Oxygenase-1
keywords: Human papillomavirus; Immunosuppression; Myeloid-derived suppressor cells; NK cells