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Tumoricidal efficacy coincides with CD11c up-regulation in antigen-specific CD8+ T cells during vaccine immunotherapy


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タイトル: Tumoricidal efficacy coincides with CD11c up-regulation in antigen-specific CD8+ T cells during vaccine immunotherapy
著者: Takeda, Yohei 著作を一覧する
Azuma, Masahiro 著作を一覧する
Matsumoto, Misako 著作を一覧する
Seya, Tsukasa 著作を一覧する
キーワード: CTL
CD11c+ CD8+ T cell
Antitumor immunotherapy
Therapeutic marker
発行日: 2016年 9月13日
出版者: BioMed Central
誌名: Journal of experimental & clinical cancer research
巻: 35
開始ページ: 143
出版社 DOI: 10.1186/s13046-016-0416-x
抄録: Background: Dendritic cells (DCs) mount tumor-associated antigens (TAAs), and the double-stranded RNA adjuvant Poly(I:C) stimulates Toll-like receptor 3 (TLR3) signal in DC, which in turn induces type I interferon (IFN) and interleukin-12 (IL-12), then cross-primes cytotoxic T lymphocytes (CTLs). Proliferation of CTLs correlates with tumor regression. How these potent cells expand with high quality is crucial to the outcome of CTL therapy. However, good markers reflecting the efficacy of DC-target immunotherapy have not been addressed. Methods: Using an EG7 (ovalbumin, OVA-positive) tumor-implant mouse model, we examined what is a good marker for active CTL induction in treatment with Poly(I:C)/OVA. Results: Simultaneous administration of Poly(I:C) and antigen (Ag) OVA significantly increased a minor population of CD8+ T cells, that express CD11c in lymphoid and tumor sites. The numbers of the CD11c+ CD8+ T cells correlated with those of induced Ag-specific CD8+ T cells and tumor regression. The CD11c+ CD8+ T cell moiety was characterized by its high killing activity and IFN-γ-producing ability, which represent an active phenotype of the effector CTLs. Not only a TLR3-specific (TICAM-1-dependent) signal but also TLR2 (MyD88) signal in DC triggered the expansion of CD11c+ CD8+ T cells in tumor-bearing mice. Notably, human CD11c+ CD8+ T cells also proliferated in peripheral blood mononuclear cells (PBMC) stimulated with cytomegalovirus (CMV) Ag. Conclusions: CD11c expression in CD8+ T cells reflects anti-tumor CTL activity and would be a marker for immunotherapeutic efficacy in mouse models and probably cancer patients as well.
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 瀬谷 司


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