Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung
Abstract Intravesical administration of Bacillus Calmette-Guérin (BCG) was one of the first FDA-approved immunotherapies and remains a standard treatment for bladder cancer. Previous studies have demonstrated that intravenous (IV) administration of BCG is well-tolerated and effective in preventing t...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41768-8 |
| _version_ | 1797558759752466432 |
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| author | Eduardo Moreo Aitor Jarit-Cabanillas Iñaki Robles-Vera Santiago Uranga Claudia Guerrero Ana Belén Gómez Pablo Mata-Martínez Luna Minute Miguel Araujo-Voces María José Felgueres Gloria Esteso Iratxe Uranga-Murillo Maykel Arias Julián Pardo Carlos Martín Mar Valés-Gómez Carlos del Fresno David Sancho Nacho Aguiló |
| author_facet | Eduardo Moreo Aitor Jarit-Cabanillas Iñaki Robles-Vera Santiago Uranga Claudia Guerrero Ana Belén Gómez Pablo Mata-Martínez Luna Minute Miguel Araujo-Voces María José Felgueres Gloria Esteso Iratxe Uranga-Murillo Maykel Arias Julián Pardo Carlos Martín Mar Valés-Gómez Carlos del Fresno David Sancho Nacho Aguiló |
| author_sort | Eduardo Moreo |
| collection | DOAJ |
| description | Abstract Intravesical administration of Bacillus Calmette-Guérin (BCG) was one of the first FDA-approved immunotherapies and remains a standard treatment for bladder cancer. Previous studies have demonstrated that intravenous (IV) administration of BCG is well-tolerated and effective in preventing tuberculosis infection in animals. Here, we examine IV BCG in several preclinical lung tumor models. Our findings demonstrate that BCG inoculation reduced tumor growth and prolonged mouse survival in models of lung melanoma metastasis and orthotopic lung adenocarcinoma. Moreover, IV BCG treatment was well-tolerated with no apparent signs of acute toxicity. Mechanistically, IV BCG induced tumor-specific CD8+ T cell responses, which were dependent on type 1 conventional dendritic cells, as well as NK cell-mediated immunity. Lastly, we also show that IV BCG has an additive effect on anti-PD-L1 checkpoint inhibitor treatment in mouse lung tumors that are otherwise resistant to anti-PD-L1 as monotherapy. Overall, our study demonstrates the potential of systemic IV BCG administration in the treatment of lung tumors, highlighting its ability to enhance immune responses and augment immune checkpoint blockade efficacy. |
| first_indexed | 2024-03-10T17:35:57Z |
| format | Article |
| id | doaj.art-cddf6509eb5149ae82e3ae71ebde6322 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:35:57Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-cddf6509eb5149ae82e3ae71ebde63222023-11-20T09:52:17ZengNature PortfolioNature Communications2041-17232023-10-0114111710.1038/s41467-023-41768-8Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lungEduardo Moreo0Aitor Jarit-Cabanillas1Iñaki Robles-Vera2Santiago Uranga3Claudia Guerrero4Ana Belén Gómez5Pablo Mata-Martínez6Luna Minute7Miguel Araujo-Voces8María José Felgueres9Gloria Esteso10Iratxe Uranga-Murillo11Maykel Arias12Julián Pardo13Carlos Martín14Mar Valés-Gómez15Carlos del Fresno16David Sancho17Nacho Aguiló18Grupo de Genética de Micobacterias, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-AragonCentro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)Grupo de Genética de Micobacterias, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-AragonGrupo de Genética de Micobacterias, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-AragonGrupo de Genética de Micobacterias, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-AragonHospital la Paz Institute for Health Research (IdiPAZ)Hospital la Paz Institute for Health Research (IdiPAZ)Grupo de Genética de Micobacterias, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-AragonDepartamento de Inmunología y Oncología, Centro Nacional de Biotecnología (CNB-CSIC)Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología (CNB-CSIC)Grupo de Inmunoterapia, Inmunidad y Cáncer, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-AragonGrupo de Inmunoterapia, Inmunidad y Cáncer, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-AragonGrupo de Inmunoterapia, Inmunidad y Cáncer, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-AragonGrupo de Genética de Micobacterias, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-AragonDepartamento de Inmunología y Oncología, Centro Nacional de Biotecnología (CNB-CSIC)Hospital la Paz Institute for Health Research (IdiPAZ)Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)Grupo de Genética de Micobacterias, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-AragonAbstract Intravesical administration of Bacillus Calmette-Guérin (BCG) was one of the first FDA-approved immunotherapies and remains a standard treatment for bladder cancer. Previous studies have demonstrated that intravenous (IV) administration of BCG is well-tolerated and effective in preventing tuberculosis infection in animals. Here, we examine IV BCG in several preclinical lung tumor models. Our findings demonstrate that BCG inoculation reduced tumor growth and prolonged mouse survival in models of lung melanoma metastasis and orthotopic lung adenocarcinoma. Moreover, IV BCG treatment was well-tolerated with no apparent signs of acute toxicity. Mechanistically, IV BCG induced tumor-specific CD8+ T cell responses, which were dependent on type 1 conventional dendritic cells, as well as NK cell-mediated immunity. Lastly, we also show that IV BCG has an additive effect on anti-PD-L1 checkpoint inhibitor treatment in mouse lung tumors that are otherwise resistant to anti-PD-L1 as monotherapy. Overall, our study demonstrates the potential of systemic IV BCG administration in the treatment of lung tumors, highlighting its ability to enhance immune responses and augment immune checkpoint blockade efficacy.https://doi.org/10.1038/s41467-023-41768-8 |
| spellingShingle | Eduardo Moreo Aitor Jarit-Cabanillas Iñaki Robles-Vera Santiago Uranga Claudia Guerrero Ana Belén Gómez Pablo Mata-Martínez Luna Minute Miguel Araujo-Voces María José Felgueres Gloria Esteso Iratxe Uranga-Murillo Maykel Arias Julián Pardo Carlos Martín Mar Valés-Gómez Carlos del Fresno David Sancho Nacho Aguiló Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung Nature Communications |
| title | Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung |
| title_full | Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung |
| title_fullStr | Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung |
| title_full_unstemmed | Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung |
| title_short | Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung |
| title_sort | intravenous administration of bcg in mice promotes natural killer and t cell mediated antitumor immunity in the lung |
| url | https://doi.org/10.1038/s41467-023-41768-8 |
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