The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients
The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients
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DOI：
10.3390/cancers11020140
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发表时间：
2019-02-01
期刊：
影响因子：
5.2
通讯作者：
Sakagami, Takuro
中科院分区：
文献类型：
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作者：
Saruwatari, Koichi;Sato, Ryo;Sakagami, Takuro
背景：抗程序性细胞死亡1 （PD-1）单克隆抗体（Abs）释放对癌症的免疫反应。然而，通过阻断PD-1/ pd配体1（PD-L1）信号通路破坏免疫检查点功能可能引发重症肌无力（MG），成为危及生命的免疫相关不良事件。MG是一种神经肌肉疾病，与抗乙酰胆碱受体（anti-AChR）抗体阳性密切相关，抗乙酰胆碱受体抗体是MG的高特异性和诊断性抗体。方法：一名72岁男性确诊为化疗难治性肺鳞状细胞癌，选择纳武单抗作为三线方案。我们描述了抗achr抗体血清阳性肺癌患者对抗pd -1抗体治疗实现持久完全缓解（CR）的第一份报告。为了进一步探讨这种情况，我们对预处理肿瘤进行了多重免疫荧光分析。结果：患者获得了持久的CR，未发生MG。然而，在抗pd -1抗体治疗的两年中，抗achr抗体水平升高。亚临床MG患者肿瘤具有高PD-L1表达和浸润性炎症肿瘤免疫微环境。结论：本研究表明，即使抗achr抗体阳性，免疫检查点抑制剂也可以安全使用，并为具有免疫“热”肿瘤的晚期癌症患者提供益处。尽管需要与神经科医生协商仔细监测临床表现，但对于无症状抗achr抗体血清阳性的癌症患者，免疫检查点抑制剂应被视为一种治疗选择。
Background: Anti-programmed cell death 1 (PD-1) monoclonal antibodies (Abs) unleash an immune response to cancer. However, a disruption of the immune checkpoint function by blocking PD-1/PD-ligand 1(PD-L1) signaling may trigger myasthenia gravis (MG) as a life-threatening immune-related adverse event. MG is a neuromuscular disease and is closely associated with being positive for anti-acetylcholine receptor (anti-AChR) Abs, which are high specific and diagnostic Abs for MG. Methods: A 72-year-old man was diagnosed with chemotherapy-refractory lung squamous cell carcinoma and nivolumab was selected as the third-line regimen. We describe the first report of an anti-AChR Ab-seropositive lung cancer patient achieving a durable complete response (CR) to an anti-PD-1 antibody therapy. To further explore this case, we performed multiplex immunofluorescence analysis on a pretreatment tumor. Results: The patient achieved a durable CR without developing MG. However, the levels of anti-AChR Abs were elevated during two years of anti-PD-1 antibody therapy. The tumor of the subclinical MG patient had high PD-L1 expression and an infiltrated-inflamed tumor immune microenvironment. Conclusions: This study suggests that immune checkpoint inhibitors can be safely used and provide the benefits for advanced cancer patients with immunologically 'hot' tumor even if anti-AChR Abs are positive. Although careful monitoring clinical manifestation in consultation with neurologist is needed, immune checkpoint inhibitors should be considered as a treatment option for asymptomatic anti-AChR Ab-seropositive cancer patients.