Odin Therapeutics, Newton, MA, 02458, USA.
Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Cell Death Dis. 2022 May 30;13(5):509. doi: 10.1038/s41419-022-04912-8.
Interest in the lysosome's potential role in anticancer therapies has recently been appreciated in the field of immuno-oncology. Targeting lysosomes triggers apoptotic pathways, inhibits cytoprotective autophagy, and activates a unique form of apoptosis known as immunogenic cell death (ICD). This mechanism stimulates a local and systemic immune response against dead-cell antigens. Stressors that can lead to ICD include an abundance of ROS which induce lysosome membrane permeability (LMP). Dying cells express markers that activate immune cells. Dendritic cells engulf the dying cell and then present the cell's neoantigens to T cells. The discovery of ICD-inducing agents is important due to their potential to trigger autoimmunity. In this review, we discuss the various mechanisms of activating lysosome-induced cell death in cancer cells specifically and the strategies that current laboratories are using to selectively promote LMP in tumors.
近年来，免疫肿瘤学领域已经意识到溶酶体在抗癌疗法中的潜在作用。靶向溶酶体可触发细胞凋亡途径，抑制细胞保护性自噬，并激活一种称为免疫原性细胞死亡（ICD）的独特形式的凋亡。这种机制刺激了针对死亡细胞抗原的局部和全身免疫反应。可导致 ICD 的应激源包括大量 ROS，其诱导溶酶体膜通透性（LMP）。垂死的细胞表达激活免疫细胞的标志物。树突状细胞吞噬垂死的细胞，然后将细胞的新抗原呈递给 T 细胞。诱导 ICD 的药物的发现很重要，因为它们有可能引发自身免疫。在这篇综述中，我们讨论了在癌细胞中激活溶酶体诱导细胞死亡的各种机制，以及当前实验室用于选择性促进肿瘤中 LMP 的策略。
