Published in:
01-07-2011 | Original article
Enhanced anti-tumor immunity by superantigen-pulsed dendritic cells
Authors:
Masato Kato, Yutaro Nakamura, Takafumi Suda, Yuichi Ozawa, Naoki Inui, Naohiro Seo, Toshi Nagata, Yukio Koide, Pawel Kalinski, Hirotoshi Nakamura, Kingo Chida
Published in:
Cancer Immunology, Immunotherapy
|
Issue 7/2011
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Abstract
Staphylococcal enterotoxins A (SEA) and B (SEB) are classical models of superantigens (SAg), which induce potent T-cell-stimulating activity by forming complexes with MHC class II molecules on antigen-presenting cells. This large-scale activation of T-cells is accompanied by increased production of cytokines such as interferon-γ (IFN-γ). Additionally, as we previously reported, IFN-γ-producing CD8+ T cells act as “helper cells,” supporting the ability of dendritic cells to produce interleukin-12 (IL-12)p70. Here, we show that DC pulsed with SAg promote the enhancement of anti-tumor immunity. Murine bone marrow-derived dendritic cells (DC) were pulsed with OVA257–264 (SIINFEKL), which is an H-2Kb target epitope of EG7 [ovalbumin (OVA)-expressing EL4] cell lines, in the presence of SEA and SEB and were subcutaneously injected into naïve C57BL/6 mice. SAg plus OVA257–264-pulsed DC vaccine strongly enhanced peptide-specific CD8+ T cells exhibiting OVA257–264-specific cytotoxic activity and IFN-γ production, leading to the induction of protective immunity against EG7 tumors. Furthermore, cyclophosphamide (CY) added to SAg plus tumor-antigens (OVA257–264, tumor lysate, or TRP-2) pulsed DC immunization markedly enhanced tumor-specific T-cell expansion and had a significant therapeutic effect against various tumors (EG7, 2LL, and B16). Superantigens are potential candidates for enhancing tumor immunity in DC vaccines.