Alshaebi Fadhl, Safi Mohammed, Algabri Yousif A, Al-Azab Mahmoud, Aldanakh Abdullah, Alradhi Mohammed, Reem Alariqi, Zhang Caiqing
Department of Respiratory, Shandong Second Provincial General Hospital, Shandong University, Jinan, Shandong, China.
Department of Biomedical Engineering, School of Control Science and Engineering, Shandong University, Jinan, Shandong, China.
Front Oncol. 2023 Jan 31;13:1099696. doi: 10.3389/fonc.2023.1099696. eCollection 2023.
Interleukin-34 (IL-34) is a cytokine that is involved in the regulation of immune cells, including macrophages, in the tumor microenvironment (TME). Macrophages are a type of immune cell that can be found in large numbers within the TME and have been shown to have a role in the suppression of immune responses in cancer. This mmune suppression can contribute to cancer development and tumors' ability to evade the immune system. Immune checkpoint inhibitors (ICIs) are a type of cancer treatment that target proteins on immune cells that act as "checkpoints," regulating the activity of the immune system. Examples of these proteins include programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). ICIs work by blocking the activity of these proteins, allowing the immune system to mount a stronger response against cancer cells. The combination of IL-34 inhibition with ICIs has been proposed as a potential treatment option for cancer due to the role of IL-34 in the TME and its potential involvement in resistance to ICIs. Inhibiting the activity of IL-34 or targeting its signaling pathways may help to overcome resistance to ICIs and improve the effectiveness of these therapies. This review summarizes the current state of knowledge concerning the involvement of IL-34-mediated regulation of TME and the promotion of ICI resistance. Besides, this work may shed light on whether targeting IL-34 might be exploited as a potential treatment option for cancer patients in the future. However, further research is needed to fully understand the mechanisms underlying the role of IL-34 in TME and to determine the safety and efficacy of this approach in cancer patients.
白细胞介素-34(IL-34)是一种细胞因子,参与肿瘤微环境(TME)中包括巨噬细胞在内的免疫细胞的调节。巨噬细胞是一种免疫细胞,在TME中大量存在,并且已被证明在癌症免疫反应抑制中发挥作用。这种免疫抑制可促进癌症发展以及肿瘤逃避免疫系统的能力。免疫检查点抑制剂(ICIs)是一种癌症治疗方法,靶向免疫细胞上作为“检查点”的蛋白质,调节免疫系统的活性。这些蛋白质的例子包括程序性细胞死亡蛋白1(PD-1)和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)。ICIs通过阻断这些蛋白质的活性起作用,使免疫系统对癌细胞产生更强的反应。由于IL-34在TME中的作用及其可能参与对ICIs的耐药性,IL-34抑制与ICIs的联合已被提议作为一种潜在的癌症治疗选择。抑制IL-34的活性或靶向其信号通路可能有助于克服对ICIs的耐药性并提高这些疗法的有效性。本综述总结了关于IL-34介导的TME调节和促进ICIs耐药性的当前知识状态。此外,这项工作可能有助于阐明靶向IL-34是否可能在未来被用作癌症患者的潜在治疗选择。然而,需要进一步研究以充分了解IL-34在TME中作用的潜在机制,并确定这种方法在癌症患者中的安全性和有效性。