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癌症是导致人类死亡的重要原因,手术、放疗和化疗等传统的癌症治疗手段已经不能满足现代癌症治疗的需求。近年来,免疫检查点抑制剂(ICIs)的发现,掀起了肿瘤免疫治疗的热潮。目前,多种免疫检查点抑制剂已经投入临床使用,如细胞毒T淋巴细胞相关抗原4 (CTLA-4 )抗体药物伊匹单抗(ipilimumab)、PD-1抑制剂帕母单抗(pembrolizumab, keytruda)和纳武单抗(nivolumab, opdivo)以及PD-L1抑制剂阿替利珠单抗(atezolizumab)、阿利库单抗(avelumab)和德瓦鲁单抗(durvalumab)。ICIs生物制剂在疗效和特异性方面的优势已经得到充分的证明,并且已经应用于多种肿瘤的治疗,如转移性黑色素瘤、非小细胞肺癌、头颈部鳞状细胞癌和霍奇金淋巴瘤[1]。但是ICIs在临床使用中仍然存在局限性,如很多接受免疫治疗的患者都经历了胃肠道毒性、内分泌毒性以及皮肤毒性等免疫相关不良事件(immune-irAEs)。除此之外,根据免疫疗法的类型以及治疗周期,患者需要支付高额的治疗费用[2]。
人们研究发现传统中药具有“扶正驱邪”的双重抗肿瘤作用。许多中药活性成分一方面能够通过破坏癌细胞的氧化还原平衡,抑制癌细胞的增殖,诱导癌细胞周期阻滞和凋亡来“驱邪”,另一方面可以通过增强机体免疫功能来“扶正”起到治疗肿瘤的作用。近年来,研究发现许多中药活性小分子可以抑制PD1/PD-L1的表达,改善肿瘤微环境(TME)的免疫抑制[3]。本文主要就抑制肿瘤免疫微环境中PD-1/PD-L1表达的中药活性小分子进行综述,希望为免疫检查点小分子抑制剂的研究提供线索。
Research progress on active ingredients from traditional Chinese medicine as inhibitors of PD-1/PD-L1 of cancer immune checkpoint
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摘要: 肿瘤免疫治疗已成为新型的癌症治疗手段,有望彻底消除肿瘤。免疫检查点抑制剂,特别是程序性死亡受体-1(PD-1)和程序性死亡受体-配体1(PD-L1)抗体在多种实体瘤的治疗中取得很好的临床疗效,但是生物制剂存在免疫原性强、价格昂贵等缺点,因此,寻找免疫检查点小分子抑制剂成为未来肿瘤免疫疗法的新挑战。本文将综述近年发现的抑制PD-1/PD-L1表达的中药活性小分子及其对肿瘤免疫微环境的调控作用。
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关键词:
- 中药活性小分子 /
- 肿瘤免疫微环境 /
- 程序性死亡受体-1 /
- 程序性死亡受体-配体1
Abstract: Tumor immunotherapy has become a new cancer treatment which has been expected to eliminate tumors. Immune checkpoint inhibitors, especially programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) antibodies, have achieved significant clinical efficacy in the treatment of solid tumors. But biologics possess disadvantages such as strong immunogenicity and high cost. Therefore, the discovery of small molecule drugs as immune checkpoint inhibitors may overcome the shortcomings of biologics and become a new challenge for future tumor immunotherapy. The active small molecules from traditional Chinese medicine that inhibit the expression of PD-1/PD-L1 and their regulatory effects on the tumor immune microenvironment were reviewed in this paper. -
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