免疫检查点抑制剂（ICI）显著改善了癌症患者的预后。然而，大多数患者会产生免疫相关的不良事件（irAEs），这可能持续存在并显著降低生活质量。神经 irAEs 发生在1-5%的患者中，可引发严重的、永久性的后遗症，甚至危及生命。为了改善神经 irAEs 的诊断和治疗，并更好地了解其发病机制，我们评估了先前神经病毒感染是否与神经 irAEs 相关联。 我们分析了来自荷兰、澳大利亚和德国的61例黑色素瘤患者，包括24例神经毒性患者和37例对照患者，以评估可能使ICI诱发神经 irAEs 的神经病毒感染。我们使用常规血清学检测评估了先前报道的14种病毒感染、6种细菌感染和1种原虫感染，这些感染已知可能引发神经病理学变化。荷兰和澳大利亚队列（NL）包括在新辅助ICI治疗（OpACIN-neo和PRADO试验；NCT02977052）中接受治疗的患者的治疗前血浆样本。在荷兰/澳大利亚队列中，总共比较了11例神经 irAEs 患者和27例对照患者（无神经 irAEs 的患者）。德国队列（LMU）包括13例出现神经 irAEs 的患者的血清样本和10例无任何记录 irAEs 的对照患者。 通过测量针对调查对象的特异性抗体，评估了神经 irAEs 与21种可能的先前感染的关联。与对照患者相比，发生神经 irAEs 的患者对测试的所有病毒（巨细胞病毒、EB病毒、带状疱疹病毒、麻疹、风疹、甲型和乙型流感病毒、人类单纯疱疹病毒6和7、单纯疱疹病毒1和2、B19病毒、A型和E型肝炎病毒和人类T淋巴病毒1和2）、细菌（Borrelia burgdorferi sensu lato、Campylobacter jejuni、Mycoplasma pneumoniae、Coxiella burnetti、幽门螺杆菌、耶尔森氏菌和假结肠耶尔森氏菌）和原虫（弓形虫）感染的血清流行率相似。因此，分析未提供证据支持所调查的病原体的血清流行率与ICI引起的神经毒性之间的关联。 在三个国家的黑色素瘤患者中，先前的病毒、细菌和原虫神经病变感染似乎与神经 irAEs 的发展无关。需要进一步努力来揭示神经 irAEs 的潜在因素，以便确定这些毒性的风险因素，特别是随着ICI在早期疾病中的使用越来越多。 © 2023. 作者。

Immune checkpoint inhibitors (ICI) substantially improve outcome for patients with cancer. However, the majority of patients develops immune-related adverse events (irAEs), which can be persistent and significantly reduce quality of life. Neurological irAEs occur in 1-5% of patients and can induce severe, permanent sequelae or even be fatal. In order to improve the diagnosis and treatment of neurological irAEs and to better understand their pathogenesis, we assessed whether previous neurotropic infections are associated with neurological irAEs.Neurotropic infections that might predispose to ICI-induced neurological irAEs were analyzed in 61 melanoma patients from 3 countries, the Netherlands, Australia and Germany, including 24 patients with neurotoxicity and 37 control patients. In total, 14 viral, 6 bacterial, and 1 protozoal infections previously reported to trigger neurological pathologies were assessed using routine serology testing. The Dutch and Australian cohorts (NL) included pre-treatment plasma samples of patients treated with neoadjuvant ICI therapy (OpACIN-neo and PRADO trials; NCT02977052). In the Dutch/Australian cohort a total of 11 patients with neurological irAEs were compared to 27 control patients (patients without neurological irAEs). The German cohort (LMU) consisted of serum samples of 13 patients with neurological irAE and 10 control patients without any documented irAE under ICI therapy.The association of neurological irAEs with 21 possible preceding infections was assessed by measuring specific antibodies against investigated agents. The seroprevalence of all the tested viral (cytomegalovirus, Epstein-Barr-Virus, varicella-zoster virus, measles, rubella, influenza A and B, human herpes virus 6 and 7, herpes simplex virus 1 and 2, parvovirus B19, hepatitis A and E and human T-lymphotropic virus type 1 and 2), bacterial (Borrelia burgdorferi sensu lato, Campylobacter jejuni, Mycoplasma pneumoniae, Coxiella burnetti, Helicobacter pylori, Yersinia enterocolitica and Y. pseudotuberculosis) and protozoal (Toxoplasma gondii) infections was similar for patients who developed neurological irAEs as compared to control patients. Thus, the analysis provided no evidence for an association of described agents tested for seroprevalence with ICI induced neurotoxicity.Previous viral, bacterial and protozoal neurotropic infections appear not to be associated with the development of neurological irAEs in melanoma patients who underwent therapy with ICI across 3 countries. Further efforts are needed to unravel the factors underlying neurological irAEs in order to identify risk factors for these toxicities, especially with the increasing use of ICI in earlier stage disease.© 2023. The Author(s).