治疗诱导衰老重塑肝细胞癌免疫微环境： 机制、耐药与治疗策略

孙 建文
白俄罗斯国立大学国际萨哈罗夫环境研究所

摘要


治疗诱导衰老（Therapy-Induced Senescence，TIS）是肝细胞癌（Hepatocellular Carcinoma，HCC）免疫
治疗研究的新方向。治疗引发的肿瘤细胞衰老一方面可以被“衰老监视”吸引T细胞、NK细胞和巨噬细胞清除
衰老细胞，起到抗肿瘤的作用；另一方面，衰老细胞以及它的衰老相关分泌表型（Senescence-Associated Secretory
Phenotype，SASP），会通过慢性炎症、募集Treg、MDSC和M2巨噬细胞等免疫抑制细胞、上调PD-1/PD-L1等免
疫检查点分子，并诱导T细胞耗竭来促进免疫逃逸和免疫治疗耐药。本文对TIS重塑HCC免疫微环境的机制、衰老
相关免疫治疗耐药以及“促衰老-清除衰老细胞-免疫治疗”的联合策略进行综述，以期给逆转HCC免疫治疗耐药
提供思路。

关键词


肝细胞癌;治疗诱导衰老;肿瘤免疫微环境;免疫治疗耐药;衰老相关分泌表型

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参考


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