文章：

肿瘤中的免疫原性细胞死亡：靶向坏死下垂诱导抗肿瘤免疫

Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity

原文发布日期：2024-03-07

DOI: 10.1038/s41568-024-00674-x

类型: Review Article

开放获取: 否

英文摘要：

Most metastatic cancers remain incurable due to the emergence of apoptosis-resistant clones, fuelled by intratumour heterogeneity and tumour evolution. To improve treatment, therapies should not only kill cancer cells but also activate the immune system against the tumour to eliminate any residual cancer cells that survive treatment. While current cancer therapies rely heavily on apoptosis — a largely immunologically silent form of cell death — there is growing interest in harnessing immunogenic forms of cell death such as necroptosis. Unlike apoptosis, necroptosis generates second messengers that act on immune cells in the tumour microenvironment, alerting them of danger. This lytic form of cell death optimizes the provision of antigens and adjuvanticity for immune cells, potentially boosting anticancer treatment approaches by combining cellular suicide and immune response approaches. In this Review, we discuss the mechanisms of necroptosis and how it activates antigen-presenting cells, drives cross-priming of CD8+ T cells and induces antitumour immune responses. We also examine the opportunities and potential drawbacks of such strategies for exposing cancer cells to immunological attacks.

摘要翻译： 

大多数转移性癌症仍无法治愈，这是由于肿瘤内异质性和肿瘤进化促进了抗凋亡克隆的出现。为改善治疗效果，疗法不仅应杀死癌细胞，还需激活免疫系统对抗肿瘤，以清除治疗后残留的癌细胞。当前癌症治疗主要依赖细胞凋亡——一种基本不引发免疫反应的细胞死亡方式——但人们对利用免疫原性细胞死亡（如坏死性凋亡）的兴趣日益增长。与凋亡不同，坏死性凋亡会产生作用于肿瘤微环境中免疫细胞的第二信使，向其发出危险警报。这种裂解性细胞死亡方式能为免疫细胞优化抗原和佐剂的呈递，通过结合细胞自杀与免疫应答机制，有望增强抗癌治疗策略。本文综述了坏死性凋亡的机制，探讨其如何激活抗原呈递细胞、驱动CD8+T细胞的交叉致敏并诱导抗肿瘤免疫应答。同时分析了此类策略在使癌细胞暴露于免疫攻击过程中的机遇与潜在缺陷。

原文链接：

Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity