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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 even...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407108/ https://www.ncbi.nlm.nih.gov/pubmed/30682845 http://dx.doi.org/10.3390/cancers11020140 |
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author | Saruwatari, Koichi Sato, Ryo Nakane, Shunya Sakata, Shinya Takamatsu, Koutaro Jodai, Takayuki Mito, Remi Horio, Yuko Saeki, Sho Tomita, Yusuke Sakagami, Takuro |
author_facet | Saruwatari, Koichi Sato, Ryo Nakane, Shunya Sakata, Shinya Takamatsu, Koutaro Jodai, Takayuki Mito, Remi Horio, Yuko Saeki, Sho Tomita, Yusuke Sakagami, Takuro |
author_sort | Saruwatari, Koichi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6407108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64071082019-03-21 The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients Saruwatari, Koichi Sato, Ryo Nakane, Shunya Sakata, Shinya Takamatsu, Koutaro Jodai, Takayuki Mito, Remi Horio, Yuko Saeki, Sho Tomita, Yusuke Sakagami, Takuro Cancers (Basel) Communication 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. MDPI 2019-01-24 /pmc/articles/PMC6407108/ /pubmed/30682845 http://dx.doi.org/10.3390/cancers11020140 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Saruwatari, Koichi Sato, Ryo Nakane, Shunya Sakata, Shinya Takamatsu, Koutaro Jodai, Takayuki Mito, Remi Horio, Yuko Saeki, Sho Tomita, Yusuke Sakagami, Takuro The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients |
title | The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients |
title_full | The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients |
title_fullStr | The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients |
title_full_unstemmed | The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients |
title_short | The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients |
title_sort | risks and benefits of immune checkpoint blockade in anti-achr antibody-seropositive non-small cell lung cancer patients |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407108/ https://www.ncbi.nlm.nih.gov/pubmed/30682845 http://dx.doi.org/10.3390/cancers11020140 |
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