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...
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MDPI AG
2019-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/2/140 |
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| author | Koichi Saruwatari Ryo Sato Shunya Nakane Shinya Sakata Koutaro Takamatsu Takayuki Jodai Remi Mito Yuko Horio Sho Saeki Yusuke Tomita Takuro Sakagami |
| author_facet | Koichi Saruwatari Ryo Sato Shunya Nakane Shinya Sakata Koutaro Takamatsu Takayuki Jodai Remi Mito Yuko Horio Sho Saeki Yusuke Tomita Takuro Sakagami |
| author_sort | Koichi Saruwatari |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T08:06:14Z |
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| language | English |
| last_indexed | 2024-03-12T08:06:14Z |
| publishDate | 2019-01-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c9bb57031f1d464c9b3b22d78764ac222023-09-02T19:32:48ZengMDPI AGCancers2072-66942019-01-0111214010.3390/cancers11020140cancers11020140The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer PatientsKoichi Saruwatari0Ryo Sato1Shunya Nakane2Shinya Sakata3Koutaro Takamatsu4Takayuki Jodai5Remi Mito6Yuko Horio7Sho Saeki8Yusuke Tomita9Takuro Sakagami10Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanDepartment of Neurology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanDepartment of Neurology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi, Kumamoto 860–8556, JapanBackground: 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.https://www.mdpi.com/2072-6694/11/2/140anti-PD-1 monoclonal antibodiesanti-acetylcholine receptor (AChR) antibodyB cellimmune checkpoint blockadeimmune-related adverse events (irAEs)myasthenia gravis (MG)non-small-cell lung cancer (NSCLC)nivolumabprogrammed cell death ligand 1 (PD-L1)T cell |
| spellingShingle | Koichi Saruwatari Ryo Sato Shunya Nakane Shinya Sakata Koutaro Takamatsu Takayuki Jodai Remi Mito Yuko Horio Sho Saeki Yusuke Tomita Takuro Sakagami The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients Cancers 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 |
| 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 | 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 |
| url | https://www.mdpi.com/2072-6694/11/2/140 |
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