Chen Allen Y, Wolchok Jedd D, Bass Anne R
Division of Rheumatology, Hospital for Special Surgery, New York, NY, USA.
New York Presbyterian Hospital, Weill Cornell Medicine, New York, NY, USA.
Nat Rev Rheumatol. 2021 Apr;17(4):213-223. doi: 10.1038/s41584-021-00584-4. Epub 2021 Mar 8.
Immune checkpoint inhibitors (ICIs) are effective in the treatment of patients with advanced cancer and have emerged as a pillar of standard cancer care. However, their use is complicated by adverse effects known as immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis. ICI-induced inflammatory arthritis is distinguished from other irAEs by its persistence and requirement for long-term treatment. TNF inhibitors are commonly used to treat inflammatory diseases such as rheumatoid arthritis, spondyloarthropathies and inflammatory bowel disease, and have also been adopted as second-line agents to treat irAEs refractory to glucocorticoid treatment. Experiencing an irAE is associated with a better antitumour response after ICI treatment. However, whether TNF inhibition can be safely used to treat irAEs without promoting cancer progression, either by compromising ICI therapy efficacy or via another route, remains an open question. In this Review, we discuss clinical and preclinical studies that address the relationship between TNF, TNF inhibition and cancer. The bulk of the evidence suggests that at least short courses of TNF inhibitors are safe for the treatment of irAEs in patients with cancer undergoing ICI therapy. Data from preclinical studies hint that TNF inhibition might augment the antitumour effect of ICI therapy while simultaneously ameliorating irAEs.
免疫检查点抑制剂（ICIs）在晚期癌症患者的治疗中有效，并已成为标准癌症治疗的支柱。然而，其使用因免疫相关不良事件（irAEs）而变得复杂，包括ICI诱导的炎性关节炎。ICI诱导的炎性关节炎因其持续性和长期治疗需求而有别于其他irAEs。肿瘤坏死因子（TNF）抑制剂常用于治疗类风湿关节炎、脊柱关节病和炎性肠病等炎性疾病，也已被用作二线药物来治疗对糖皮质激素治疗难治的irAEs。经历irAE与ICI治疗后更好的抗肿瘤反应相关。然而，TNF抑制是否能安全用于治疗irAEs而不促进癌症进展，无论是通过损害ICI治疗疗效还是通过其他途径，仍是一个悬而未决的问题。在本综述中，我们讨论了涉及TNF、TNF抑制与癌症之间关系的临床和临床前研究。大量证据表明，至少短期使用TNF抑制剂对接受ICI治疗的癌症患者治疗irAEs是安全的。临床前研究数据提示，TNF抑制可能增强ICI治疗的抗肿瘤作用，同时改善irAEs。
