Department of Immunology, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Pharmacology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
Daru. 2019 Dec;27(2):879-884. doi: 10.1007/s40199-019-00295-y. Epub 2019 Aug 21.
Our knowledge of the role of innate immunity in protecting against cancers has expanded greatly in recent years. An early focus was on the adoptive transfer of natural killer (NK) cells and, although this approach has demonstrated promising results in many patients, a few limitations including immune escape of tumors from cytotoxic killing by NK cells have caused treatment failures. Downregulation of the expression of activating ligands on the surface of cancer cells and prevention of the activity of soluble factors are among the mechanisms employed by cancer cells to overcome NK-mediated immunity. It has become evident that a class of small membranous structures of endosomal origin known as exosomes play a key role in regulating the local tumor microenvironment. Here we hypothesize that exosome secretion by cancer cells, which is greater than that of normal cells, is an important escape mechanism employed by cancer cells. Interruption of exosome release by various inhibitory agents in combination with the adoptive transfer of NK cells may overcome, at least in part, the treatment failures that occur with adoptive NK cell transfer. In this regard, repositioning of approved drugs with previously shown effects on exosome release may be a good strategy to bypass the safety issues of newly identified agents and will also dramatically reduce the huge costs of drug approval process.
近年来，我们对先天免疫在预防癌症方面的作用的认识有了很大的提高。早期的重点是自然杀伤 (NK) 细胞的过继转移，尽管这种方法在许多患者中显示出了有前景的结果，但一些局限性，包括 NK 细胞对癌细胞的细胞毒性杀伤的免疫逃逸，导致了治疗失败。癌细胞用来克服 NK 介导的免疫的机制包括癌细胞表面激活配体的下调和可溶性因子活性的预防。显然，一类来源于内体的小膜状结构，称为外泌体，在外周免疫耐受中起着关键作用。在这里，我们假设癌细胞的外泌体分泌比正常细胞更多，是癌细胞采用的一种重要逃逸机制。通过各种抑制剂中断外泌体的释放，并结合 NK 细胞的过继转移，可能至少部分克服过继 NK 细胞转移中出现的治疗失败。在这方面，重新定位已被证明具有外泌体释放作用的已批准药物可能是一种很好的策略，可以避免新确定药物的安全性问题，同时也将大大降低药物批准过程的巨大成本。
