The Janus Face of Death Receptor Signaling during Tumor Immunoediting.
The Janus Face of Death Receptor Signaling during Tumor Immunoediting.
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DOI：
10.3389/fimmu.2016.00446
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发表时间：
2016
影响因子：
7.3
通讯作者：
Szegezdi E
中科院分区：
文献类型：
--
作者：
O' Reilly E;Tirincsi A;Logue SE;Szegezdi E
肿瘤免疫监测对抑制癌变至关重要。恶性转化细胞可以通过不同的机制被先天免疫系统和适应性免疫系统识别。免疫效应细胞通过表达肿瘤坏死因子配体家族中的死亡配体细胞因子，诱导肿瘤细胞外源性死亡。然而，一些肿瘤细胞可以逃避免疫消除而发展。通过将表达死亡配体的效应细胞切割成低活性形式、死亡受体的突变或沉默、诱骗受体和促生存蛋白的过表达，可以获得对死亡配体诱导的凋亡途径的抗性。尽管免疫系统在消除恶性转化细胞方面非常有效，但异常/功能失调的死亡配体信号传导抑制了其细胞毒性。此外，dr还可以传递促生存和促迁移信号。因此，功能失调的死亡受体介导的凋亡/坏死凋亡信号不仅对细胞死亡提供被动抵抗，而且积极驱动肿瘤细胞的运动、侵袭，并有助于随后的转移。这篇综述讨论了死亡受体信号在肿瘤免疫编辑过程的早期、消除阶段和晚期、逃逸阶段的双重贡献。死亡受体激动剂仍然具有潜在的癌症治疗潜力，因为它们可以在没有激活针对肿瘤的免疫系统的情况下执行肿瘤消除免疫效应功能。本文还讨论了将死亡受体激动剂发展成为有效的癌症治疗药物的机遇和挑战。
Cancer immune surveillance is essential for the inhibition of carcinogenesis. Malignantly transformed cells can be recognized by both the innate and adaptive immune systems through different mechanisms. Immune effector cells induce extrinsic cell death in the identified tumor cells by expressing death ligand cytokines of the tumor necrosis factor ligand family. However, some tumor cells can escape immune elimination and progress. Acquisition of resistance to the death ligand-induced apoptotic pathway can be obtained through cleavage of effector cell expressed death ligands into a poorly active form, mutations or silencing of the death receptors, or overexpression of decoy receptors and pro-survival proteins. Although the immune system is highly effective in the elimination of malignantly transformed cells, abnormal/dysfunctional death ligand signaling curbs its cytotoxicity. Moreover, DRs can also transmit pro-survival and pro-migratory signals. Consequently, dysfunctional death receptor-mediated apoptosis/necroptosis signaling does not only give a passive resistance against cell death but actively drives tumor cell motility, invasion, and contributes to consequent metastasis. This dual contribution of the death receptor signaling in both the early, elimination phase, and then in the late, escape phase of the tumor immunoediting process is discussed in this review. Death receptor agonists still hold potential for cancer therapy since they can execute the tumor-eliminating immune effector function even in the absence of activation of the immune system against the tumor. The opportunities and challenges of developing death receptor agonists into effective cancer therapeutics are also discussed.
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DOI：
10.1007/s00018-016-2191-4
发表时间：
2016-06
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Dondelinger Y;Darding M;Bertrand MJ;Walczak H
通讯作者：
Walczak H
DOI：
10.1042/bj20100814
发表时间：
2010-09-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Altieri DC
通讯作者：
Altieri DC
影响因子：
8.8
作者：
Dondelinger, Yves;Declercq, Wim;Vandenabeele, Peter
通讯作者：
Vandenabeele, Peter
影响因子：
14.2
作者：
Campbell, Kerry S.;Hasegawa, Jun
通讯作者：
Hasegawa, Jun
影响因子：
4.4
作者：
Cretney, E;Takeda, K;Smyth, MJ
通讯作者：
Smyth, MJ