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β-defensin 2 as an Adjuvant Promotes Anti-Melanoma Immune Responses and Inhibits the Growth of Implanted Murine Melanoma In Vivo
Author(s) -
Han-fang Mei,
Xiaobao Jin,
Jiayong Zhu,
Ai-hua Zeng,
Qiang Wu,
Xuemei Lu,
Xiaobo Li,
Juan Shen
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0031328
Subject(s) - defensin , cd8 , immune system , immunotherapy , adjuvant , biology , vaccination , immunology , ctl* , melanoma , cancer research , cytotoxic t cell , in vivo , immunity , innate immune system , microbiology and biotechnology , in vitro , antimicrobial , biochemistry
β-defensin 2 is a small antimicrobial peptide of the innate immune system and has been thought to regulate anti-tumor immunity. However, little is known on whether β-defensin 2 could modulate melanoma-specific NK and T cell responses. In this study, we first cloned the murine β-defensin 2 gene by RT-PCR and generated the β-defensin 2 stably expressing B16 cells (B16-mBD2). Subsequently, we evaluated whether vaccination with irradiated B16-mBD2 could modulate the growth of implanted B16 cells and determined the potential mechanisms underlying the action of B16-mBD2 vaccine in modulating the growth of B16 tumors in C57BL/6. We found that vaccination with irradiated B16-mBD2, but not with control B16-p or parental B16, inhibited the development and progression of B16 tumors, and prolonged the survival of tumor-bearing mice. However, vaccination with irradiated B16-mBD2 failed to inhibit the development of B16 tumors in the CD4 + - or CD8 + -depleted recipients. Furthermore, vaccination with irradiated B16-mBD2 stimulated strong NK activity and promoted potent B16-specific CTL responses, accompanied by augmenting IFN-γ and IL-12, but not IL-4, responses in the recipient mice. Moreover, vaccination with irradiated B16-mBD2 promoted the infiltration of CD8 + and CD4 + T, NK cells and macrophages in the tumor tissues. These data suggest β-defensin 2 may act as a positive regulator, promoting anti-tumor NK and T cell responses in vivo . Therefore, β-defensin 2 may be used for the development of immunotherapy for the intervention of melanoma.

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