Macroautophagy/autophagy is a highly conserved evolutionary mechanism involving lysosomes for the degradation of cytoplasmic components including organelles. The constitutive, basal level of autophagy is fundamental for preserving cellular homeostasis; however, alterations in autophagy can cause disease pathogenesis, including cancer. The role of autophagy in cancer is particularly complicated, since this process acts both as a tumor suppressor in precancerous stages but facilitates tumor progression during carcinogenesis and later stages of cancer progression. This shift between anti-tumor and pro-tumor roles may be influenced by genetic and environmental factors modulating key pathways such as those involving autophagy-related proteins, the PI3K-AKT-MTOR axis, and AMPK, which often show dysregulation in tumors. Autophagy regulates various cellular functions, including metabolism of glucose, glutamine, and lipids, cell proliferation, metastasis, and several types of cell death (apoptosis, ferroptosis, necroptosis and immunogenic cell death). These multifaceted roles demonstrate the potential of autophagy to affect DNA damage repair, cell death pathways, proliferation and survival, which are critical in determining cancer cells’ response to chemotherapy. Therefore, targeting autophagy pathways presents a promising strategy to combat chemoresistance, as one of the major reasons for the failure in cancer patient treatment. Furthermore, autophagy modulates immune evasion and the function of immune cells such as T cells and dendritic cells, influencing the tumor microenvironment and cancer’s biological behavior. However, the therapeutic targeting of autophagy is complex due to its dual role in promoting survival and inducing cell death in cancer cells, highlighting the need for strategies that consider both the beneficial and detrimental effects of autophagy modulation in cancer therapy. Hence, both inducers and inhibitors of autophagy have been introduced for the treatment of cancer. This review emphasizes the intricate interplay between autophagy, tumor biology, and immune responses, offering insights into potential therapeutic approaches that deploy autophagy in the cancer suppression.

中文翻译：

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癌症发展、免疫逃避和耐药性中的自噬


巨自噬/自噬是一种高度保守的进化机制，涉及溶酶体降解细胞质成分（包括细胞器）。自噬的组成型基础水平是维持细胞稳态的基础;然而，自噬的改变可导致疾病发病机制，包括癌症。自噬在癌症中的作用特别复杂，因为这个过程既在癌前阶段充当肿瘤抑制因子，又在癌症进展的后期促进肿瘤进展。这种抗肿瘤和促肿瘤作用之间的转变可能受到调节关键通路的遗传和环境因素的影响，例如涉及自噬相关蛋白、PI3K-AKT-MTOR 轴和 AMPK 的通路，这些通路通常在肿瘤中表现出失调。自噬调节各种细胞功能，包括葡萄糖、谷氨酰胺和脂质的代谢、细胞增殖、转移和几种类型的细胞死亡（细胞凋亡、铁死亡、坏死性凋亡和免疫原性细胞死亡）。这些多方面的作用证明了自噬影响 DNA 损伤修复、细胞死亡途径、增殖和存活的潜力，这对于决定癌细胞对化疗的反应至关重要。因此，靶向自噬途径提供了一种有前途的对抗化疗耐药的策略，这是癌症患者治疗失败的主要原因之一。此外，自噬调节免疫逃避和 T 细胞和树突状细胞等免疫细胞的功能，影响肿瘤微环境和癌症的生物行为。 然而，自噬的治疗靶向很复杂，因为它在促进癌细胞存活和诱导细胞死亡方面具有双重作用，这突出了考虑癌症治疗中自噬调节的有益和有害影响的策略的必要性。因此，自噬的诱导剂和抑制剂都已被引入用于治疗癌症。这篇综述强调了自噬、肿瘤生物学和免疫反应之间错综复杂的相互作用，为在癌症抑制中部署自噬的潜在治疗方法提供了见解。