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細胞自噬與腫瘤微環境的研究進展

RECENT INSIGHTS INTO THE FUNCTION OF AUTOPHAGY IN THE TUMOR MICROENVIRONMENT

摘要


細胞自噬是細胞內物質汰換的重要過程之一,在一些損壞的蛋白質和胞器的形成中,透過雙重膜結構的自噬囊泡包裝後,到溶酶體降解和回收利用。細胞自噬對於維持細胞穩定性具有正面作用。然而,許多因子(如缺氧)引發的自噬並預防癌症是普遍的現象。根據腫瘤類型、進程及遺傳條件,自噬可以作為抗腫瘤因子或促腫瘤因子。其中,惡性腫瘤是發現與自噬相關的最早疾病之一,自噬在癌症發生和發展的不同階段有不同的分子調控機制。因此,腫瘤自噬的所扮演的角色是研究的核心問題。近期發現自噬在多種機制中,使對抗腫瘤免疫失效,導致腫瘤從免疫細胞攻擊中逃脫。這種作用誘發抗自噬的調控,並克服腫瘤免疫監測的全新途徑,這也是目前發展癌症免疫療法的重大挑戰。在本篇回顧,將討論自噬在腫瘤微環境中所扮演的角色及最新的研究進展,特別是自噬如何對抗腫瘤免疫反應。

並列摘要


Cell autophagy is one of the important material flow processes in the cell. Some of the damaged proteins and organelles were embedding by the double membrane structure of autophagy vesicles package, then, to the lysosome degradation and recycling. Autophagy has a positive role in the maintenance of cell homeostasis. However, autophagy deregulation caused by several stress factors, such as hypoxia, which is prevalent in many cancers. It is well established autophagy can act as a tumor suppressor or tumor promoter depending on the tumor type, stage, and genetic context. Among them, the malignant tumor is one of the earliest diseases found to be associated with autophagy. Autophagy has different effects in different stages of the occurrence and development of cancer. Therefore, the duality of autophagy in tumors is the central area of study about tumors. Emerging evidence points to the prominent role of autophagy in disabling the antitumor immune response by multiple overlapping mechanisms leading to tumor escape from immune cell attack mediated by both natural killer cells and cytotoxic T-lymphocytes. Such a role has inspired significant interest in applying anti-autophagy therapies as an entirely new approach to overcome tumor escape from immune surveillance, which so far constitutes a major challenge in developing more effective cancer immunotherapies. Here, we discuss recent developments in the role of autophagy in tumor microenvironment how autophagy can lead to an anti-tumor immune response.

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