The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients

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

Alveolar Epithelial Denudation Is a Major Factor in the Pathogenesis of Pleuroparenchymal Fibroelastosis

The pathogenesis of pleuroparenchymal fibroelastosis (PPFE), a rare interstitial lung disease, remains unclear. Based on previous reports and our experience, we hypothesized that alveolar epithelial denudation (AED) was involved in the pathogenesis of PPFE. This multicenter retrospective study investigated the percentage of AED and the features of the denudated areas in 26 PPFE cases, 30 idiopathic pulmonary fibrosis (IPF) cases, and 29 controls. PPFE patients had lower forced vital capacities and higher residual volume/total lung capacities in pulmonary function tests compared to IPF and control patients. Histopathologically, subpleural fibroelastosis was observed in PPFE, and AED was observed in 12.01% of cases in the subpleural or interlobular septa regardless of fibroelastosis. The percentage of AED in the PPFE group was significantly higher than that in the IPF group (6.84%; p = 0.03) and the normal group (1.19%; p < 0.001). In the IPF group, the percentage of AED and the presence of PPFE-like lesions in the upper lobes were examined radiologically, but no correlation was found. We showed that AED frequently occurred in PPFE. AED was less frequent in IPF, which, in combination with imaging data, suggests that PPFE may have a different pathogenesis from IPF