title: A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy.
abstract: A key factor in dendritic cell (DC)-based tumor immunotherapy is the identification of an immunoadjuvant capable of inducing DC maturation to enhance cellular immunity. The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tumor immunotherapy, and its capacity for inducing DC maturation was investigated. In this study, we showed that Rv0652 is recognized by Toll-like receptor 4 (TLR4) to induce DC maturation, and pro-inflammatory cytokine production (TNF-alpha, IL-1beta, and IL-6) that is partially modulated by both MyD88 and TRIF signaling pathways. Rv0652-activated DCs could activate naïve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-gamma, and induce T cell-mediated-cytotoxicity. Immunization of mice with Rv0652-stimulated ovalbumin (OVA)-pulsed DCs resulted in induction of a potent OVA-specific CD8+ T cell response, slowed tumor growth, and promoted long-term survival in a murine OVA-expressing E.G7 thymoma model. These findings suggest that Rv0652 enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation, and that Rv0652 may be an effective adjuvant for enhancing the therapeutic response to DC-based tumor immunotherapy.
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju, South Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju, South Korea.
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Medicine, Korea University, Seoul, South Korea.
authors.forename: Min-Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju, South Korea.
authors.forename: Tae Heung
authors.initials: TH
authors.lastname: Kang
authors.affiliation: Department of Physiology, School of Medicine, Kangwon National University, Chuncheon, South Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Medicine, Seonam University, Namwon, Jeonbuk, South Korea.
authors.forename: Byoung Yul
authors.initials: BY
authors.lastname: Soh
authors.affiliation: Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental & Bioresources Sciences, Chonbuk National University, Iksan, South Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
authors.forename: Yong Kyoo
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Department of Agricultural Biotechnology, and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Han Wool
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology, and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju, South Korea.
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju, South Korea.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D007167:Immunotherapy; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D016207:Cytokines; D051197:Toll-Like Receptor 4; C476286:Ticam1 protein, mouse; C493487:Tlr4 protein, mouse
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