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Reinstalling Antitumor Immunity by Inhibiting Tumor-Derived Immunosuppressive Molecule IDO through RNA Interference

2006; American Association of Immunologists; Volume: 177; Issue: 8 Linguagem: Inglês

10.4049/jimmunol.177.8.5639

1550-6606

Xiufen Zheng, James Koropatnick, Mu Li, Xusheng Zhang, Fengjun Ling, Xiubao Ren, Xishan Hao, Hongtao Sun, Costin Vladau, Jacob Franek, Biao Feng, Bradley L. Urquhart, Robert Zhong, David J. Freeman, Bertha García, Wei-Ping Min,

Immunotherapy and Immune Responses

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.