T cell-mediated additive cytotoxicity - death by multiple bullets.
T cell-mediated additive cytotoxicity - death by multiple bullets.
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DOI：
10.1016/j.trecan.2022.07.007
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发表时间：
2022-08
期刊：
影响因子：
18.4
通讯作者：
B. Weigelin;P. Friedl
中科院分区：
文献类型：
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作者：
B. Weigelin;P. Friedl
免疫效应细胞（包括细胞毒性T细胞（CTL））通过直接细胞-细胞接触诱导细胞凋亡并消除靶细胞。在体内，CTL不能通过单独接触有效地杀死实体瘤细胞，而是依赖于许多CTL的多击相互作用（群集）。最近的证据表明，CTL的多击相互作用在靶细胞中诱导一系列亚致死性损伤事件，包括穿孔素介导的膜损伤、活性氧（ROS）的诱导、核膜破裂和DNA损伤。单个损伤可以修复，但当以快速顺序诱导时，亚致死性损伤可以累积并诱导靶细胞死亡。在这里，我们总结了CTL诱导和其他细胞应激的亚致死损伤和细胞毒性的概念，并讨论了改善免疫治疗和多靶点抗癌治疗的意义。
Immune effector cells, including cytotoxic T cells (CTLs), induce apoptosis and eliminate target cells by direct cell–cell contacts.In vivo, CTLs fail to efficiently kill solid tumor cells by individual contacts but rely upon multihit interactions by many CTLs (swarming). Recent evidence has indicated that multihit interactions by CTLs induce a series of sublethal damage events in target cells, including perforin-mediated membrane damage, induction of reactive oxygen species (ROS), nuclear envelope rupture, and DNA damage. Individual damage can be repaired, but when induced in rapid sequence, sublethal damage can accumulate and induce target cell death. Here, we summarize the sublethal damage and additive cytotoxicity concepts for CTL-induced and other cell stresses and discuss the implications for improving immunotherapy and multitargeted anticancer therapies.