Concepts and mechanisms underlying chemotherapy induced immunogenic cell death: impact on clinical studies and considerations for combined therapies.
Concepts and mechanisms underlying chemotherapy induced immunogenic cell death: impact on clinical studies and considerations for combined therapies.
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DOI：
10.18632/oncotarget.6113
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发表时间：
2015-12-08
期刊：
影响因子：
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通讯作者：
Johnston B
中科院分区：
文献类型：
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作者：
Gebremeskel S;Johnston B
化疗历来被认为以免疫原性沉默的方式诱导癌细胞死亡。然而，最近的研究表明，特定化疗药物（如蒽环类药物）的治疗结果与它们在癌细胞中诱导免疫原性细胞死亡（ICD）过程的能力密切相关。这个过程会产生一系列信号，刺激免疫系统识别并清除肿瘤细胞。大量研究表明，化疗诱导的ICD是通过钙网蛋白（CALR）、ATP、趋化因子（C-X-C基序）配体10 （CXCL10）和高迁移率组盒1 （HMGB1）的暴露/释放发生的。本综述深入探讨了CALR暴露、toll样受体3/IFN/CXCL10轴的激活以及死亡癌细胞中ATP和HMGB1的释放的概念和机制。在临床研究中影响ICD效果的因素以及化疗与免疫治疗联合治疗的设计也进行了讨论。
Chemotherapy has historically been thought to induce cancer cell death in an immunogenically silent manner. However, recent studies have demonstrated that therapeutic outcomes with specific chemotherapeutic agents (e.g. anthracyclines) correlate strongly with their ability to induce a process of immunogenic cell death (ICD) in cancer cells. This process generates a series of signals that stimulate the immune system to recognize and clear tumor cells. Extensive studies have revealed that chemotherapy-induced ICD occurs via the exposure/release of calreticulin (CALR), ATP, chemokine (C–X–C motif) ligand 10 (CXCL10) and high mobility group box 1 (HMGB1). This review provides an in-depth look into the concepts and mechanisms underlying CALR exposure, activation of the Toll-like receptor 3/IFN/CXCL10 axis, and the release of ATP and HMGB1 from dying cancer cells. Factors that influence the impact of ICD in clinical studies and the design of therapies combining chemotherapy with immunotherapy are also discussed.