Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Saruwatari, Koichi, Sato, Ryo, Nakane, Shunya, Sakata, Shinya, Takamatsu, Koutaro, Jodai, Takayuki, Mito, Remi, Horio, Yuko, Saeki, Sho, Tomita, Yusuke, Sakagami, Takuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783401475689414656
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
work_keys_str_mv AT saruwatarikoichi therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT satoryo therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT nakaneshunya therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT sakatashinya therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT takamatsukoutaro therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT jodaitakayuki therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT mitoremi therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT horioyuko therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT saekisho therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT tomitayusuke therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT sakagamitakuro therisksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT saruwatarikoichi risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT satoryo risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT nakaneshunya risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT sakatashinya risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT takamatsukoutaro risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT jodaitakayuki risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT mitoremi risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT horioyuko risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT saekisho risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT tomitayusuke risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients
AT sakagamitakuro risksandbenefitsofimmunecheckpointblockadeinantiachrantibodyseropositivenonsmallcelllungcancerpatients