Immunogenic Cell Death: A Step Ahead of Autophagy in Cancer Therapy.
Immunogenic Cell Death: A Step Ahead of Autophagy in Cancer Therapy.
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DOI：
10.33696/cancerimmunol.3.041
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Chen H
中科院分区：
文献类型：
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作者：
Gupta G;Borglum K;Chen H
免疫原性细胞死亡 (ICD) 通过长期暴露于肿瘤微环境 (TME) 中的损伤相关分子模式 (DAMP)，在提供持久的保护性抗肿瘤免疫方面发挥着重要作用。 DAMP 对于吸引免疫原性细胞至 TME、DC 成熟以及将肿瘤抗原正确呈递给 T 细胞至关重要，以便它们能够杀死更多癌细胞。因此，为了 DAMP 的正确释放，细胞死亡的受控机制是必要的。药物诱导的肿瘤细胞杀伤是通过细胞凋亡发生的，其中自噬可以充当保护肿瘤细胞的屏障，有时还可以提供对化疗药物的多药耐药性。然而，自噬对于 ATP 的释放是必需的，因为它仍然是诱导 ICD 的关键 DAMP 之一。在这篇综述中，我们讨论了自噬和细胞凋亡之间复杂的平衡，以及我们可以应用的各种策略来使这些免疫沉默过程产生免疫原性。自噬和细胞凋亡有几个步骤可以通过调节来产生免疫反应。参与该过程的基因可以通过药物或抑制剂来调节，以放大 ICD 的效果，因此可以作为潜在的治疗靶点。
Immunogenic cell death (ICD) plays a major role in providing long lasting protective antitumor immunity by the chronic exposure of damage associated molecular patterns (DAMPs) in the tumor microenvironment (TME). DAMPs are essential for attracting immunogenic cells to the TME, maturation of DCs, and proper presentation of tumor antigens to the T cells so they can kill more cancer cells. Thus for the proper release of DAMPs, a controlled mechanism of cell death is necessary. Drug induced tumor cell killing occurs by apoptosis, wherein autophagy may act as a shield protecting the tumor cells and sometimes providing multi-drug resistance to chemotherapeutics. However, autophagy is required for the release of ATP as it remains one of the key DAMPs for the induction of ICD. In this review, we discuss the intricate balance between autophagy and apoptosis and the various strategies that we can apply to make these immunologically silent processes immunogenic. There are several steps of autophagy and apoptosis that can be regulated to generate an immune response. The genes involved in the processes can be regulated by drugs or inhibitors to amplify the effects of ICD and therefore serve as potential therapeutic targets.