The extrinsic RNA-sensing pathway for adjuvant immunotherapy of cancer.
Infection with RNA viruses presents a typical pattern of virus products, double-stranded RNA (dsRNA), and induces the maturation of antigen-presenting dendritic cell (mDC). There are several dsRNA sensors that are differentially distributed on the cell membrane and in the cytoplasm and are variably expressed depending on the cell type. Among these sensors, TLR3 links to the adaptor TICAM-1 (TRIF), which is characterized by its unique multipronged signaling cascades for cytokine/chemokine production, apoptosis and autophagy in both immune and tumor cells. In the context of mDC maturation, various cellular events are further induced in response to dsRNA; these include cross-priming followed by CD8+ CTL induction, NK activation and proliferation of CD4+ T cells including Th1, Th2, Treg and Th17 cells. In this review, we focus on the potential role of dsRNA in modulating the inflammatory milieu around mDCs and tumor-associated antigens to drive specific cellular effectors against the tumor.
Seya
Tsukasa
T
Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Japan. seya-tu@pop.med.hokudai.ac.jp
Matsumoto
Misako
M
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D000276:Adjuvants, Immunologic; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D011070:Poly I-C / Q000276:immunology / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D012330:RNA, Double-Stranded; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition; D011070:Poly I-C