title: Reinstalling antitumor immunity by inhibiting tumor-derived immunosuppressive molecule IDO through RNA interference.
abstract: Tumor-derived immune suppression is a major impediment to successful immune/gene cancer therapy. In the present study, we describe a novel strategy to disrupt tumor-derived immune suppression by silencing a tolerogenic molecule of tumor origin, IDO, using small interfering RNA (siRNA). Silencing of IDO in B16F10 cells in vitro using IDO-siRNA prevented catabolism of tryptophan and inhibited apoptosis of T cells. IDO-siRNA treatment of B16F10 cells in vitro inhibited subsequent growth, tumor formation, and the size of tumor formed, by those cells when transplanted into host mice. In vivo treatment of B16F10 tumor-bearing mice successfully postponed tumor formation time and significantly decreased tumor size. Furthermore, in vivo IDO-siRNA treatment resulted in recovery of T cells responses and enhancement of tumor-specific killing. Thus, silencing IDO may break tumor-derived immune suppression. These data indicate that RNA interference has potential to enhance cancer therapy by reinstalling anticancer immunity.
authors.affiliation: Department of Surgery, Pathology, Oncology, Microbiology, and Immunology, London Health Science Centre, London, Ontario, Canada.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zheng
authors.forename: James
authors.initials: J
authors.lastname: Koropatnick
authors.forename: Mu
authors.initials: M
authors.lastname: Li
authors.forename: Xusheng
authors.initials: X
authors.lastname: Zhang
authors.forename: Fengjun
authors.initials: F
authors.lastname: Ling
authors.forename: Xiubao
authors.initials: X
authors.lastname: Ren
authors.forename: Xishan
authors.initials: X
authors.lastname: Hao
authors.forename: Hongtao
authors.initials: H
authors.lastname: Sun
authors.forename: Costin
authors.initials: C
authors.lastname: Vladau
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Franek
authors.forename: Biao
authors.initials: B
authors.lastname: Feng
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Urquhart
authors.forename: Robert
authors.initials: R
authors.lastname: Zhong
authors.forename: David J
authors.initials: DJ
authors.lastname: Freeman
authors.forename: Bertha
authors.initials: B
authors.lastname: Garcia
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Min
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014364:Tryptophan / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D034741:RNA, Small Interfering; D014364:Tryptophan