Inhibiting the Inhibitor in Synovial Macrophages and Cancer Immunotherapy-Associated Inflammatory Arthritis.
Inhibiting the Inhibitor in Synovial Macrophages and Cancer Immunotherapy-Associated Inflammatory Arthritis.
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抑制滑膜巨噬细胞和癌症免疫治疗相关炎症性关节炎中的抑制剂。
DOI：
10.1002/art.42743
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Bottini,Nunzio
中科院分区：
文献类型：
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作者：
Shah,NisargJ;Bottini,Nunzio
免疫检查点抑制剂（ICI）疗法的有效性改变了癌症治疗，并使长期有效的疾病控制成为可能。然而，医源性免疫相关不良事件（irAE）可能会限制治疗的有效性。 1 在 irAE 中，风湿性表现较常见，并且接受 PD-1 或 CTLA-4+ PD-1 ICI 联合治疗的患者中有 3-5% 发生炎症性关节炎 (IA)，通常与其他 irAE 一起出现。 2 IA-irAE 患者可能会出现糜烂性疾病、滑膜炎和关节积液，即使 ICI 治疗停止后，IA-irAE 也可能持续存在3。由于 ICI 治疗会阻断 T 细胞激活的抑制信号，因此研究重点关注 ICI 引发的致病性 T 细胞的潜在作用。 CTLA-4+ PD-1 ICI 治疗与滑液和血液中 T 辅助细胞 (Th) 17 细胞特征的增强有关。 Th17 的积累与银屑病关节炎和幼年特发性关节炎中的类似观察结果相似4, 5。然而，IA-irAE 也与关节和外周血中 1 型干扰素激活的 CD38hiCD127-CD8+ T 细胞的积累有关，这与其他自身免疫性关节病没有相关性。 6 虽然迄今为止的研究正在帮助阐明 T 细胞在 IA-irAE 中的作用，但其他免疫细胞亚群的参与仍不完全清楚。
The effectiveness of immune checkpoint inhibitor (ICI) therapy has transformed cancer management and enabled the possibility of long-term effective disease control. However, iatrogenic immune-related adverse events (irAEs) can limit the effectiveness of treatment. 1 Among irAEs, rheumatic manifestations are frequent and inflammatory arthritis (IA) occurs in 3-5% of patients receiving either PD-1 or combination CTLA-4+ PD-1 ICI therapy, often manifesting together with other irAEs. 2 Patients with IA-irAE can experience erosive disease, synovitis and joint effusion and IA-irAE can persist even after cessation of ICI therapy3.Because ICI therapy blocks inhibitory signals of T cell activation, studies have focused on the potential role of ICI-elicited pathogenic T cells. CTLA-4+ PD-1 ICI therapy has been associated with enhanced T helper cell (Th) 17 cell signatures in both synovial fluid and blood. This accumulation of Th17 parallels similar observations in psoriatic arthritis and juvenile idiopathic arthritis4, 5. However, IA-irAE has been also associated with an accumulation of type 1 interferon activated CD38hiCD127-CD8+ T cells in the joints and peripheral blood, which does not have correlates with other autoimmune arthropathies. 6 While studies thus far are helping elucidate the role of T cells in IA-irAE, the participation of other immune cell subsets remains incompletely understood.