Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung

Moreo, Eduardo (Universidad de Zaragoza) ; Jarit-Cabanillas, Aitor ; Robles-Vera, Iñaki ; Uranga, Santiago (Universidad de Zaragoza) ; Guerrero, Claudia (Universidad de Zaragoza) ; Gómez, Ana Belén (Universidad de Zaragoza) ; Mata-Martínez, Pablo ; Minute, Luna ; Araujo-Voces, Miguel ; Felgueres, María José ; Esteso, Gloria ; Uranga-Murillo, Iratxe ; Arias, Maykel ; Pardo, Julián (Universidad de Zaragoza) ; Martín, Carlos (Universidad de Zaragoza) ; Valés-Gómez, Mar ; del Fresno, Carlos ; Sancho, David ; Aguiló, Nacho (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/s41467-023-41768-8

Año: 2023

Publicado en: Nature communications 14, 1 (2023), 690[ 17 pp]
ISSN: 2041-1723

Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP50-21
Financiación: info:eu-repo/grantAgreement/EC/H2020/725091/EU/Functional characterisation of mitochondrial metabolic adaptations to innate sensing in dendritic cell subsets/MITOMAD
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CB21-13-100087
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CP20-00106
Financiación: info:eu-repo/grantAgreement/EUR/MCIN/AEI/CPP2021-008310
Financiación: info:eu-repo/grantAgreement/ES/MCINN/PID2021-123795OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-108157RB
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-097625-B-100

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Microbiología (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Área Inmunología (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Proy. investigación HQA (Dpto. Microb.Ped.Radio.Sal.Pú.)