Tumor necrosis factor superfamily signaling: life and death in cancer.

IF 7.7 2区医学 Q1 ONCOLOGY Cancer and Metastasis Reviews Pub Date : 2024-12-01 Epub Date: 2024-10-04 DOI:10.1007/s10555-024-10206-6

Obada Ababneh, Daisuke Nishizaki, Shumei Kato, Razelle Kurzrock

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Abstract

Immune checkpoint inhibitors have shaped the landscape of cancer treatment. However, many patients either do not respond or suffer from later progression. Numerous proteins can control immune system activity, including multiple tumor necrosis factor (TNF) superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) members; these proteins play a complex role in regulating cell survival and death, cellular differentiation, and immune system activity. Notably, TNFSF/TNFRSF molecules may display either pro-tumoral or anti-tumoral activity, or even both, depending on tumor type. Therefore, TNF is a prototype of an enigmatic two-faced mediator in oncogenesis. To date, multiple anti-TNF agents have been approved and/or included in guidelines for treating autoimmune disorders and immune-related toxicities after immune checkpoint blockade for cancer. A confirmed role for the TNFSF/TNFRSF members in treating cancer has proven more elusive. In this review, we highlight the cancer-relevant TNFSF/TNFRSF family members, focusing on the death domain-containing and co-stimulation members and their signaling pathways, as well as their complicated role in the life and death of cancer cells.

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肿瘤坏死因子超家族信号传导：癌症中的生与死。

免疫检查点抑制剂改变了癌症治疗的格局。然而，许多患者要么没有反应，要么病情恶化。许多蛋白质可以控制免疫系统的活动，包括多种肿瘤坏死因子（TNFSF）超家族（TNFSF）和TNF受体超家族（TNFRSF）成员；这些蛋白质在调节细胞存活和死亡、细胞分化和免疫系统活动方面发挥着复杂的作用。值得注意的是，根据肿瘤类型的不同，TNFSF/TNFRSF 分子既可能具有促肿瘤活性，也可能具有抗肿瘤活性，甚至两者兼而有之。因此，TNF 是肿瘤发生过程中神秘的双面介质的原型。迄今为止，多种抗 TNF 药物已被批准和/或纳入指南，用于治疗自身免疫性疾病和免疫检查点阻断治疗癌症后的免疫相关毒性。事实证明，TNFSF/TNFRSF 成员在治疗癌症中的作用尚未得到证实。在这篇综述中，我们将重点介绍与癌症相关的 TNFSF/TNFRSF 家族成员，重点是含死亡结构域和协同刺激成员及其信号通路，以及它们在癌细胞生死过程中的复杂作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer and Metastasis Reviews 医学-肿瘤学

CiteScore

17.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Contemporary biomedical research is on the threshold of an era in which physiological and pathological processes can be analyzed in increasingly precise and mechanistic terms.The transformation of biology from a largely descriptive, phenomenological discipline to one in which the regulatory principles can be understood and manipulated with predictability brings a new dimension to the study of cancer and the search for effective therapeutic modalities for this disease. Cancer and Metastasis Reviews provides a forum for critical review and discussion of these challenging developments. A major function of the journal is to review some of the more important and interesting recent developments in the biology and treatment of malignant disease, as well as to highlight new and promising directions, be they technological or conceptual. Contributors are encouraged to review their personal work and be speculative.