Immunomodulatory effects of dsRNA and its potential as vaccine adjuvant.
dsRNA can be detected by pattern recognition receptors, for example, TLR3, MDA-5, NLRP3 to induce proinflammatory cytokines responsible for innate/adaptive immunity. Recognized by endosomal TLR3 in myeloid DCs (mDCs), dsRNA can activate mDCs into mature antigen presenting cells (mAPCs) which in turn present antigen epitopes with MHC-I molecules to naïve T cells. Coadministration of protein and synthetic dsRNA analogues can elicit an antigen-specific Th1-polarized immune response which stimulates the CD8+ CTL response and possibly dampen Th17 response. Synthetic dsRNA analogues have been tested as vaccine adjuvant against viral infections in animal models. However, a dsRNA receptor, TLR3 can be expressed in tumor cells while other members of TLR family, for example, TLR4 and TLR2 have been shown to promote tumor progression, metastasis, and chemoresistance. Thus, the promising potential of dsRNA analogues as a tumor therapeutic vaccine adjuvant should be evaluated cautiously.
Jin
Bo
B
Department of Digestive Diseases, Naval General Hospital, 6 Fucheng Rd., Beijing 100048, China. bjbo.jin@gmail.com
Sun
Tao
T
Yu
Xiao-Hong
XH
Liu
Chao-Qun
CQ
Yang
Ying-Xiang
YX
Lu
Ping
P
Fu
Shan-Feng
SF
Qiu
Hui-Bin
HB
Yeo
Anthony E T
AE
D056704:Adaptive Immunity / Q000187:drug effects; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology*; D012330:RNA, Double-Stranded / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007155:Immunologic Factors; D012330:RNA, Double-Stranded