Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan.
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, CA, USA.
Cancer Metastasis Rev. 2024 Dec;43(4):1137-1163. doi: 10.1007/s10555-024-10206-6. Epub 2024 Oct 4.
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.
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，要么后来病情进展。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（TNF）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，TNFSF/TNFRSF 分子可能表现出促肿瘤或抗肿瘤活性，甚至两者兼有，具体取决于肿瘤类型。因此，TNF 是肿瘤发生中一种神秘的两面介质的原型。迄今为止，已有多种抗 TNF 药物被批准并/或纳入指南，用于治疗自身免疫性疾病和癌症免疫检查点阻断后的免疫相关毒性。TNFSF/TNFRSF 成员在治疗癌症方面的作用已被证实更加难以捉摸。在这篇综述中，我们重点介绍了与癌症相关的 TNFSF/TNFRSF 家族成员，聚焦于含死亡结构域和共刺激成员及其信号通路，以及它们在癌细胞生死中的复杂作用。
