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Cancers 2019, 11(2), 140; https://doi.org/10.3390/cancers11020140

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

1
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, Japan
2
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, Japan
3
Department of Molecular Neurology and Therapeutics, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, Japan
*
Author to whom correspondence should be addressed.
The authors contributed equally to this work.
Received: 30 December 2018 / Revised: 18 January 2019 / Accepted: 21 January 2019 / Published: 24 January 2019
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Abstract

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. View Full-Text
Keywords: anti-PD-1 monoclonal antibodies; anti-acetylcholine receptor (AChR) antibody; B cell; immune checkpoint blockade; immune-related adverse events (irAEs); myasthenia gravis (MG); non-small-cell lung cancer (NSCLC); nivolumab; programmed cell death ligand 1 (PD-L1); T cell anti-PD-1 monoclonal antibodies; anti-acetylcholine receptor (AChR) antibody; B cell; immune checkpoint blockade; immune-related adverse events (irAEs); myasthenia gravis (MG); non-small-cell lung cancer (NSCLC); nivolumab; programmed cell death ligand 1 (PD-L1); T cell
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Saruwatari, K.; Sato, R.; Nakane, S.; Sakata, S.; Takamatsu, K.; Jodai, T.; Mito, R.; Horio, Y.; Saeki, S.; Tomita, Y.; Sakagami, T. The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients. Cancers 2019, 11, 140.

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