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PLoS One. 2014 Aug 7;9(8):e104351. doi: 10.1371/journal.pone.0104351. eCollection 2014.

A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy.

Author information

1
Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju, South Korea.
2
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.
3
Department of Physiology, College of Medicine, Korea University, Seoul, South Korea.
4
Department of Physiology, School of Medicine, Kangwon National University, Chuncheon, South Korea.
5
Department of Biochemistry, College of Medicine, Seonam University, Namwon, Jeonbuk, South Korea.
6
Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental & Bioresources Sciences, Chonbuk National University, Iksan, South Korea.
7
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
8
Department of Agricultural Biotechnology, and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.

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.

PMID:
25102137
PMCID:
PMC4125215
DOI:
10.1371/journal.pone.0104351
[Indexed for MEDLINE]
Free PMC Article
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