The tumor necrosis factor (TNF) family, which includes 19 ligands and 29 receptors, influences cellular proliferation, differentiation, and apoptosis. The TNF family plays a crucial role in the pathogenesis of Hodgkin lymphoma (HL), particularly through its influence on the tumor microenvironment (TME). Hodgkin Reed–Sternberg (HRS) cells, the hallmark of classic HL (cHL), exhibit overexpression of TNF receptor family members such as CD30 and CD40. Given the critical roles of CD30 and CD40 in the survival and proliferation of HRS cells within the TME, targeting these TNF receptors represents a promising therapeutic strategy; therapies that target CD30 have already shown efficacy in clinical settings. The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis plays a crucial role in immune evasion by HRS cells, which express PD-L1 that interacts with PD-1 on T cells, leading to T cell exhaustion and a diminished immune response against the tumor. By blocking this interaction, checkpoint inhibitors such as nivolumab and pembrolizumab have demonstrated high response rates in patients with cHL, particularly in those who have not responded to conventional therapies. The integration of immune checkpoint inhibitors (ICIs) with standard chemotherapy regimens has improved outcomes for patients with advanced-stage cHL. By understanding how TNF signaling interacts with immune checkpoints, researchers can design more effective treatment regimens that simultaneously target multiple pathways. Combining TNF inhibitors with checkpoint blockade therapies may enhance the overall anti-tumor response by addressing both direct tumor signaling and the immune evasion mechanisms employed by tumor cells.
肿瘤坏死因子（TNF）家族包含19种配体和29种受体，对细胞增殖、分化及凋亡具有重要调控作用。该家族在霍奇金淋巴瘤（HL）的发病机制中扮演关键角色，尤其通过影响肿瘤微环境（TME）发挥作用。经典霍奇金淋巴瘤（cHL）的标志性霍奇金-里德-斯特恩伯格（HRS）细胞过度表达CD30、CD40等TNF受体家族成员。鉴于CD30和CD40在TME中调控HRS细胞存活与增殖的核心作用，靶向这些TNF受体已成为极具前景的治疗策略；其中靶向CD30的疗法已在临床实践中显现疗效。程序性死亡受体-1（PD-1）/程序性死亡配体-1（PD-L1）信号轴是HRS细胞实现免疫逃逸的关键机制：HRS细胞表达的PD-L1与T细胞表面的PD-1结合，导致T细胞耗竭并削弱抗肿瘤免疫应答。通过阻断该相互作用，纳武利尤单抗和帕博利珠单抗等免疫检查点抑制剂在cHL患者（尤其对常规治疗无应答者）中展现出高应答率。将免疫检查点抑制剂（ICIs）与标准化疗方案联合应用，显著改善了晚期cHL患者的临床结局。通过解析TNF信号与免疫检查点的交互机制，研究者可设计同时靶向多通路的高效治疗方案。将TNF抑制剂与检查点阻断疗法联用，有望通过协同作用于肿瘤直接信号传导和免疫逃逸机制，全面提升抗肿瘤应答。
肿瘤(癌症)患者之家