A TLR3-Specific Adjuvant Relieves Innate Resistance to PD-L1 Blockade without Cytokine Toxicity in Tumor Vaccine Immunotherapy.

Takeda, Yohei; Kataoka, Keisuke; Yamagishi, Junya; Ogawa, Seishi; Seya, Tsukasa; Matsumoto, Misako

A TLR3-Specific Adjuvant Relieves Innate Resistance to PD-L1 Blockade without Cytokine Toxicity in Tumor Vaccine Immunotherapy.

Takeda, Yohei; Kataoka, Keisuke; Yamagishi, Junya et al.

Cell Reports, 2017, 19(9), 1874-1887

Permalink : https://hdl.handle.net/2115/70698

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/70698
タイトル	A TLR3-Specific Adjuvant Relieves Innate Resistance to PD-L1 Blockade without Cytokine Toxicity in Tumor Vaccine Immunotherapy.
著者	Takeda, Yohei ; Kataoka, Keisuke ; Yamagishi, Junya ; Ogawa, Seishi ; Seya, Tsukasa ; Matsumoto, Misako
著者名 Takeda, Yohei
著者名 Kataoka, Keisuke
e-Rad_Researcher 80535328 著者名 Yamagishi, Junya
著者名 Ogawa, Seishi
e-Rad_Researcher 10301805 著者名 Seya, Tsukasa
e-Rad_Researcher 30332456 著者名 Matsumoto, Misako
言語	英語
キーワード	cancer immunotherapy
	double-stranded RNA
	innate immunity
	PD-L1 blockade
	priming adjuvant
	Toll-like receptor 3
	tumor-associated antigen
	tumor immunity
	vaccine immunotherapy
発行日	2017-05-30
出版者	Elsevier
収録物名	Cell Reports
巻(号)	19(9)
ページ	1874-1887
抄録	Cancer patients having anti-programmed cell death-1 (PD-1)/PD ligand 1 (L1)-unresponsive tumors may benefit from advanced immunotherapy. Double-stranded RNA triggers dendritic cell (DC) maturation to cross-prime antigen-specific cytotoxic T lymphocytes (CTLs) via Toll-like receptor 3 (TLR3). The TLR3-specific RNA agonist, ARNAX, can induce anti-tumor CTLs without systemic cytokine/interferon (IFN) production. Here, we have developed a safe vaccine adjuvant for cancer that effectively implements anti-PD-L1 therapy. Co-administration of ARNAX with a tumor-associated antigen facilitated tumor regression in mouse models, and in combination with anti-PD-L1 antibody, activated tumor-specific CTLs in lymphoid tissues, enhanced CTL infiltration, and overcame anti-PD-1 resistance without cytokinemia. The TLR3-TICAM-1-interferon regulatory factor (IRF)3-IFN-β axis in DCs exclusively participated in CD8+ T cell cross-priming. ARNAX therapy established Th1 immunity in the tumor microenvironment, upregulating genes involved in DC/T cell/natural killer (NK) cell recruitment and functionality. Human ex vivo studies disclosed that ARNAX+antigen induced antigen-specific CTL priming and proliferation in peripheral blood mononuclear cells (PBMCs), supporting the feasibility of ARNAX for potentiating anti-PD-1/PD-L1 therapy in human vaccine immunotherapy.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	2211-1247
関連情報	PMID 28564605
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1016/j.celrep.2017.05.015