title: β-defensin 2 as an adjuvant promotes anti-melanoma immune responses and inhibits the growth of implanted murine melanoma in vivo.
abstract: 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.
authors.affiliation: Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, China.
authors.forename: Han-fang
authors.initials: HF
authors.lastname: Mei
authors.forename: Xiao-bao
authors.initials: XB
authors.lastname: Jin
authors.forename: Jia-yong
authors.initials: JY
authors.lastname: Zhu
authors.forename: Ai-hua
authors.initials: AH
authors.lastname: Zeng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Lu
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Shen
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D019496:Cancer Vaccines; D049109:Cell Proliferation; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D023083:beta-Defensins / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; C117047:Defb2 protein, mouse; D023083:beta-Defensins