title: Combination of all-trans retinoic acid and a human papillomavirus therapeutic vaccine suppresses the number and function of immature myeloid cells and enhances antitumor immunity.
abstract: Despite advances in the development of human papillomavirus (HPV) prophylactic vaccines, little progress has been made in the field of therapeutic vaccines in recent years. In the present study, we found a significant accumulation of immature myeloid cells (ImC) in large TC-1 tumors and demonstrated that a HPV therapeutic vaccine restored antitumor immune responses with the correction of aberrant myeloid cell differentiation by all-trans retinoic acid (ATRA). Our study demonstrated that combining ATRA with vaccination not only decreased the number of Gr-1+ CD11b+ ImC, but for the first time also suppressed the function of Gr-1+ CD11b+ ImC with decreased expression of CD80. Furthermore, large numbers of CD11c+ CD80+, CD11c+ CD86+, and CD11c+ MHCII+ mature dendritic cells were recruited. The combination therapy generated significantly increased numbers of functional E7-specific T cells with elevated interferon- secretion and enhanced cytotoxic T-cell activity. These findings suggest potential clinical benefits for the combined use of ATRA and HPV therapeutic vaccines.
authors.affiliation: Department of Cellular and Molecular Biology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Song
authors.forename: Dongxia
authors.initials: D
authors.lastname: Ye
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cui
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhao
authors.forename: Linan
authors.initials: L
authors.lastname: Yi
authors.forename: Jianming
authors.initials: J
authors.lastname: Liang
authors.forename: Jietao
authors.initials: J
authors.lastname: Song
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qingzheng
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D015153:Blotting, Western; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014212:Tretinoin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D039481:CD11b Antigen; D053918:Papillomavirus Vaccines; D014212:Tretinoin