title: Enhanced anti-tumor immunity by superantigen-pulsed dendritic cells.
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 OVA(257-264) (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 OVA(257-264)-pulsed DC vaccine strongly enhanced peptide-specific CD8(+) T cells exhibiting OVA(257-264)-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 (OVA(257-264), 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.
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kato
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.forename: Naohiro
authors.initials: N
authors.lastname: Seo
authors.forename: Toshi
authors.initials: T
authors.lastname: Nagata
authors.forename: Yukio
authors.initials: Y
authors.lastname: Koide
authors.forename: Pawel
authors.initials: P
authors.lastname: Kalinski
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Kingo
authors.initials: K
authors.lastname: Chida
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D018089:Superantigens / Q000276:immunology*; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014407:Tumor Cells, Cultured; D022223:Vaccines, Subunit / Q000627:therapeutic use
chemical_list: D018906:Antineoplastic Agents, Alkylating; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C485882:Lancl1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D018089:Superantigens; D022223:Vaccines, Subunit; D018664:Interleukin-12; D007371:Interferon-gamma; D003520:Cyclophosphamide; D010047:Ovalbumin