Double-stranded RNA promotes CTL-independent tumor cytolysis mediated by CD11b+Ly6G+ intratumor myeloid cells through the TICAM-1 signaling pathway

Shime, Hiroaki; Matsumoto, Misako; Seya, Tsukasa

Double-stranded RNA promotes CTL-independent tumor cytolysis mediated by CD11b+Ly6G+ intratumor myeloid cells through the TICAM-1 signaling pathway

Shime, Hiroaki; Matsumoto, Misako; Seya, Tsukasa

Cell Death and Differentiation, 2017, 24(3), 385-396

Permalink : https://hdl.handle.net/2115/67075

このアイテムのアクセス数:852件（2026-08-14 05:57 集計）

閲覧可能ファイル

ファイル	フォーマット	サイズ	閲覧回数	説明
22160_1_merged_1473263873_HUSCAP	pdf	3.55 MB	644
SupplementaryFigure1	jpg	557 KB	100	Supplementary Figure 1
SupplementaryFigure2	jpg	1.49 MB	352	Supplementary Figure 2
SupplementaryFigure3	jpg	1.11 MB	118	Supplementary Figure 3
SupplementaryFigure4	jpg	1.42 MB	138	Supplementary Figure 4
SupplementaryFigure5	jpg	1.93 MB	155	Supplementary Figure 5
SupplementaryFigure6	jpg	2.67 MB	122	Supplementary Figure 6
SupplementaryFigure7	jpg	911 KB	127	Supplementary Figure 7
SupplementaryFigure8	jpg	1.26 MB	112	Supplementary Figure 8
SupplementaryFigure9	jpg	728 KB	148	Supplementary Figure 9
SupplementaryTable1	jpg	317 KB	110	Supplementary Table 1

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権	open access
URI	https://hdl.handle.net/2115/67075
タイトル	Double-stranded RNA promotes CTL-independent tumor cytolysis mediated by CD11b+Ly6G+ intratumor myeloid cells through the TICAM-1 signaling pathway
その他のタイトル	CD11b+Ly6G+ cells induced by dsRNA
著者	Shime, Hiroaki ; Matsumoto, Misako ; Seya, Tsukasa
e-Rad_Researcher 70372133 著者名 Shime, Hiroaki
e-Rad_Researcher 30332456 著者名 Matsumoto, Misako
e-Rad_Researcher 10301805 著者名 Seya, Tsukasa
言語	英語
キーワード	Toll-like receptor
	tumor-associated myeloid cells
	TICAM-1 (TRIF)
	ROS/RNS
	type-I IFNs
発行日	2017-03
出版者	Nature Publishing Group
収録物名	Cell Death and Differentiation
巻(号)	24(3)
ページ	385-396
抄録	PolyI:C, a synthetic double-stranded RNA analog, acts as an immune-enhancing adjuvant that regresses tumors via cytotoxic T lymphocyte (CTL)-dependent and CTL-independent fashions, the latter of which remains largely unknown. Tumors contain CD11b+Ly6G+ cells, granulocytic myeloid-derived suppressor cells (G-MDSCs), or tumor-associated neutrophils (TANs), which play a critical role in tumor progression and development. Here, we demonstrate that CD11b+Ly6G+ cells respond to polyI:C and exhibit tumoricidal activity in an EL4 tumor implant model. PolyI:C-induced inhibition of tumor growth was attributed to caspase-8/3 cascade activation in tumor cells, which occurred independently of CD8α+/CD103+ dendritic cells (DCs) and CTLs. CD11b+Ly6G+ cells acted as anti-tumor effectors because depletion of CD11b+Ly6G+ cells totally abrogated tumor regression and caspase activation after polyI:C treatment. CD11b+Ly6G+ cells that had been activated with polyI:C showed cytotoxicity and inhibition of tumor growth through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS). These responses were abolished in either toll/interleukin-1 receptor domain-containing adaptor molecule-1 (TICAM-1)-/- or interferon (IFN)-αβ receptor 1 (IFNAR1)-/- mice. Thus, our results suggest that polyI:C targets myeloid cells in tumors, where CD11b+Ly6G+ cells exhibit anti-tumor activity through TLR3/TICAM-1 and IFNAR pathways, independent of those in CD8α+/CD103+ DCs that prime CTLs.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	1350-9047
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1038/cdd.2016.131