Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Oncologist. 2019 Aug;24(8):1013-1021. doi: 10.1634/theoncologist.2018-0633. Epub 2019 May 14.
Safe use of immune checkpoint blockade in patients with cancer and autoimmune disorders requires a better understanding of the pathophysiology of immunologic activation. We describe the immune correlates of reactivation of granulomatosis with polyangiitis (GPA)-an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis-in a patient with metastatic urothelial carcinoma treated with pembrolizumab. After PD-1 blockade, an inflammatory pulmonary nodule demonstrated a granulomatous, CD4+ T-cell infiltrate, correlating with increased CD4+ and CD8+ naïve memory cells in the peripheral blood without changes in other immune checkpoint receptors. Placed within the context of the existing literature on GPA and disease control, our findings suggest a key role for PD-1 in GPA self-tolerance and that selective strategies for immunotherapy may be needed in patients with certain autoimmune disorders. We further summarize the current literature regarding reactivation of autoimmune disorders in patients undergoing immune checkpoint blockade, as well as potential immunosuppressive strategies to minimize the risks of further vasculitic reactivation upon rechallenge with anti-PD-1 blockade. KEY POINTS: Nonspecific imaging findings in patients with cancer and rheumatological disorders may require biopsy to distinguish underlying pathology.Patients with rheumatologic disorders have increased risk of reactivation with PD-(L)1 immune checkpoint blockade, requiring assessment of disease status before starting treatment.Further study is needed to evaluate the efficacy of treatment regimens in preventing and controlling disease reactivation.
安全使用免疫检查点抑制剂治疗癌症和自身免疫性疾病患者，需要更好地了解免疫激活的病理生理学。我们描述了接受 pembrolizumab 治疗的转移性尿路上皮癌患者中，粒细胞血管炎（GPA）-抗中性粒细胞胞质抗体（ANCA）相关血管炎复发的免疫相关性。PD-1 阻断后，表现为炎症性肺结节的肉芽肿性 CD4+T 细胞浸润，与外周血中 CD4+和 CD8+幼稚记忆细胞增加相关，而其他免疫检查点受体无变化。将这些发现置于 GPA 和疾病控制的现有文献背景下，我们认为 PD-1 在 GPA 自身耐受中起关键作用，并且在某些自身免疫性疾病患者中可能需要针对免疫治疗的选择性策略。我们进一步总结了目前关于接受免疫检查点阻断的患者中自身免疫性疾病复发的文献，以及在重新接受抗 PD-1 阻断时最小化进一步血管炎再激活风险的潜在免疫抑制策略。要点：癌症和风湿性疾病患者的非特异性影像学发现可能需要活检以区分潜在的病理。患有风湿性疾病的患者在接受 PD-（L）1 免疫检查点抑制剂治疗时，再激活的风险增加，需要在开始治疗前评估疾病状态。需要进一步研究来评估治疗方案在预防和控制疾病再激活方面的疗效。
