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

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/67075

Title: Double-stranded RNA promotes CTL-independent tumor cytolysis mediated by CD11b+Ly6G+ intratumor myeloid cells through the TICAM-1 signaling pathway
Other Titles: CD11b+Ly6G+ cells induced by dsRNA
Authors: Shime, Hiroaki Browse this author →KAKEN DB
Matsumoto, Misako Browse this author →KAKEN DB
Seya, Tsukasa Browse this author →KAKEN DB
Keywords: Toll-like receptor
tumor-associated myeloid cells
TICAM-1 (TRIF)
ROS/RNS
type-I IFNs
Issue Date: Mar-2017
Publisher: Nature Publishing Group
Journal Title: Cell Death and Differentiation
Volume: 24
Issue: 3
Start Page: 385
End Page: 396
Publisher DOI: 10.1038/cdd.2016.131
Abstract: 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.
Type: article (author version)
URI: http://hdl.handle.net/2115/67075
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 瀬谷 司

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