Department of Immunology, Institute for Biological Research Sinisa Stankovic, Belgrade University, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
Immunol Res. 2012 Apr;52(1-2):157-68. doi: 10.1007/s12026-012-8284-8.
Development of resistance to TRAIL-induced toxicity is one of the strategies used from tumor cells to escape destruction from the immune system. This process may occur through aberrant expression of functional receptors, overexpression of decoy receptors on tumor cell membrane, or malfunctioning of downstream signals triggered by specific ligation of TRAIL. Numerous cytostatic, but also noncytostatic, drugs like protease inhibitors and NO-hybridized molecules have been shown to revert sensitivity of neoplastic cells to TRAIL by means of different mechanisms. This paper will review the possible routes of reconstitution of sensitivity to TRAIL-mediated immune response by specific modulation of different signals responsible for the development of resistance at both the membrane and the intracellular levels. Moreover, we will review and suggest novel strategies, aimed at resetting immune cell efficiency in cancer treatment.
肿瘤细胞产生耐药性是其逃避免疫系统破坏的策略之一。这种耐药性的产生可能是由于功能性受体的异常表达、肿瘤细胞膜上诱饵受体的过表达，或者是 TRAIL 特异性结合所触发的下游信号通路失活。蛋白酶抑制剂和 NO 杂合分子等多种细胞抑制剂和非细胞抑制剂已被证明可通过不同的机制使肿瘤细胞对 TRAIL 重新敏感。本文综述了通过特异性调节膜和细胞内水平的不同信号，恢复对 TRAIL 介导的免疫反应敏感性的可能途径。此外，我们还将回顾和提出新的策略，旨在恢复免疫细胞在癌症治疗中的效率。
