In recent years, immune checkpoint inhibitors (ICIs) have become a viable option for many cancer patients, including specific subgroups of pediatric patients. Despite their efficiency in treating different types of cancer, ICIs are responsible for a number of immune-related adverse events, including inflammatory toxicities, that can affect several organs. However, our knowledge of the impact of ICIs on the testis and male fertility is limited. It is possible that ICI treatment affects testicular function and spermatogenesis either directly or indirectly (or both). Treatment with ICIs may cause increased inflammation and immune cell infiltration within the seminiferous tubules of the testis, disturbing spermatogenesis or testosterone deficiency (primary hypogonadism). Additionally, the interference of ICIs with the hypothalamic–pituitary–gonadal axis may alter testosterone production, affecting testicular function (secondary hypogonadism) and spermatogenesis. This review provides an overview of the available evidence on the potential association between ICIs and the disruption of spermatogenesis, with special focus on ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1). Moreover, it highlights the need for further investigations and encourages the discussion of associated risks and fertility-preservation considerations between clinicians and patients.
近年来，免疫检查点抑制剂已成为包括特定儿童亚群在内的众多癌症患者的可行治疗选择。尽管该疗法在治疗多种癌症类型中展现出显著疗效，但也会引发一系列免疫相关不良事件，包括可能累及多器官的炎症性毒性反应。然而，目前关于免疫检查点抑制剂对睾丸及男性生育力影响的认识仍较为有限。该治疗可能通过直接或间接途径（或两者兼有）影响睾丸功能与精子发生过程。免疫检查点抑制剂的使用可能导致睾丸生精小管内炎症反应加剧及免疫细胞浸润，从而干扰精子发生或引发睾酮缺乏（原发性性腺功能减退）。此外，该药物对下丘脑-垂体-性腺轴的干扰可能改变睾酮生成，进而影响睾丸功能（继发性性腺功能减退）与精子发生。本综述系统梳理了现有关于免疫检查点抑制剂与精子发生障碍潜在关联的证据，特别聚焦于靶向细胞毒性T淋巴细胞相关蛋白4、程序性死亡蛋白1及其配体的抑制剂。同时，本文强调需开展深入研究，并倡导临床医生与患者就相关风险及生育力保存方案进行充分讨论。
肿瘤(癌症)患者之家