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摘要
最近成功的检查点阻断抗体引发了癌症免疫治疗的革命。检查点抑制激活适应性免疫系统,导致对一系列肿瘤类型产生持久的应答,尽管这种应答仅限于存在肿瘤浸润T细胞的患者群体。刺激免疫系统引发抗肿瘤反应的策略备受关注,目前有几个研究小组正致力于开发激活模式识别受体(PRRs)的药物,PRRs是一种能够检测致病性和损伤相关分子并通过激活先天免疫反应来做出反应的蛋白质。尽管早期的研究主要集中在膜结合PRRs的Toll样受体(TLR)家族上,但TLR的激活已被证实与促肿瘤和抗肿瘤作用相关。尽管如此,在一系列临床试验中,TLR激动剂已被作为潜在的抗癌药物使用。最近,随着早期临床数据的出现,IFN基因(STING)的细胞质PRR刺激因子(cytosolic PRR刺激物)作为另一个有前景的抗癌药物开发靶点引起了人们的关注。除了STING,其他几个细胞内PRR靶点也引起了药物研发界的兴趣,包括RIG-Ilike受体(RLRs)和nod样受体(NLRs)。在这篇综述中,我们描述了PRRs激活剂作为抗癌治疗药物的前景,并对比了早期TLR激动剂与细胞内PRR激活剂的研究进展,包括作为单一药物和与其他癌症免疫疗法联合使用。
关键词: 免疫肿瘤学,先天免疫,模式识别受体,癌症免疫治疗,TLRs
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