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Cancers (Basel). 2019 Jan 24;11(2). pii: E140. doi: 10.3390/cancers11020140.

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

Author information

1
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. rmkqq751@ybb.ne.jp.
2
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. ryosato.1981@gmail.com.
3
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. nakaneshunya@gmail.com.
4
Department of Molecular Neurology and Therapeutics, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. nakaneshunya@gmail.com.
5
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. sakata-1027@hotmail.co.jp.
6
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. takamakt@gmail.com.
7
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. jojojojojody@gmail.com.
8
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. candypinkcolor@yahoo.co.jp.
9
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. yu1980327@yahoo.co.jp.
10
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. saeshow@wg7.so-net.ne.jp.
11
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. y-tomita@kumadai.jp.
12
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860⁻8556, Japan. stakuro@kumamoto-u.ac.jp.

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.

KEYWORDS:

B cell; T cell; anti-PD-1 monoclonal antibodies; anti-acetylcholine receptor (AChR) antibody; immune checkpoint blockade; immune-related adverse events (irAEs); myasthenia gravis (MG); nivolumab; non-small-cell lung cancer (NSCLC); programmed cell death ligand 1 (PD-L1)

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