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

Seung Jun Lee, Sung Jae Shin, Moon Hee Lee, Min-Goo Lee, Tae Heung Kang, Won Sun Park, Byoung Yul Soh, Jung Hee Park, Yong Kyoo Shin, Han Wool Kim, Cheol Heui Yun, In Duk Jung, Yeong Min Park

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21 Citations (Scopus)

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.

Original languageEnglish
Article numbere104351
JournalPLoS One
Volume9
Issue number8
DOIs
Publication statusPublished - 2014 Aug 7

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Lee, S. J., Shin, S. J., Lee, M. H., Lee, M-G., Kang, T. H., Park, W. S., Soh, B. Y., Park, J. H., Shin, Y. K., Kim, H. W., Yun, C. H., Jung, I. D., & Park, Y. M. (2014). A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy. PLoS One, 9(8), [e104351]. https://doi.org/10.1371/journal.pone.0104351