Division of Medical Oncology, Washington University in Saint Louis, 660 South Euclid Avenue, Saint Louis, MO, 63110, USA.
Department of Ophthalmology and Neurology, Saint Louis University, St Louis, MO, USA.
Cancer Immunol Immunother. 2021 Sep;70(9):2497-2502. doi: 10.1007/s00262-021-02875-x. Epub 2021 Feb 5.
Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome that involves the production of autoantibodies which can cross-react with retinal epitopes leading to visual symptoms. Autoantibodies can target intracellular proteins, and only a few are directed against membrane proteins. This discrepancy in autoantibody-protein target can translate into different immune responses (T-cell mediated vs B-cell mediated). Historically, treatment of MAR has focused on surgical reduction or immunosuppressive medication, mainly glucocorticoids. However, tumor resection is not relevant in metastatic melanoma in which MAR is mostly encountered. Moreover, the use of glucocorticoids can reduce the efficacy of immunotherapy. We report the first case to our knowledge with subjective resolution of visual symptoms and objective evidence of normalization of electroretinogram of MAR with undetectable autoantibodies after administration of programmed death-1 (PD-1) inhibitor (pembrolizumab) without the use of surgical reduction or systemic immunosuppression. This case highlights the potential improvement and resolution of negative autoantibody MAR with the use of PD-1 inhibitors and emphasizes the importance of multidisciplinary approach and team discussion to avoid interventions that can decrease immunotherapy-mediated anti-tumor effect.
黑色素瘤相关视网膜病变(MAR)是一种副肿瘤综合征,涉及自身抗体的产生,这些自身抗体可以与视网膜表位发生交叉反应,导致视觉症状。自身抗体可以靶向细胞内蛋白,只有少数针对膜蛋白。这种自身抗体-蛋白靶标的差异可以转化为不同的免疫反应(T 细胞介导与 B 细胞介导)。历史上,MAR 的治疗重点是手术减少或免疫抑制药物治疗,主要是糖皮质激素。然而,在转移性黑色素瘤中,肿瘤切除术与 MAR 无关,而 MAR 主要发生在转移性黑色素瘤中。此外,糖皮质激素的使用会降低免疫疗法的疗效。我们报告了首例我们所知的病例,在使用程序性死亡-1(PD-1)抑制剂(pembrolizumab)后,MAR 的视觉症状主观缓解,视网膜电图客观证据正常,自身抗体检测不到,且未使用手术减少或全身免疫抑制。该病例强调了使用 PD-1 抑制剂可改善和缓解负性自身抗体 MAR,并强调了多学科方法和团队讨论的重要性,以避免干预措施降低免疫治疗介导的抗肿瘤作用。