Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung.
Eduardo MoreoAitor Jarit-CabanillasIñaki Robles-VeraSantiago UrangaClaudia GuerreroAna Belén GómezPablo Mata-MartínezLuna MinuteMiguel Araujo-VocesMaría José FelgueresGloria EstesoIratxe Uranga-MurilloMaykel AriasJulian PardoCarlos MartinMar Valés-GómezCarlos Del Fresno SánchezDavid SanchoNacho AguilóPublished in: Nature communications (2023)
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.
Keyphrases
- dendritic cells
- immune response
- magnetic resonance imaging
- mycobacterium tuberculosis
- randomized controlled trial
- dna damage
- computed tomography
- type diabetes
- hepatitis b virus
- metabolic syndrome
- magnetic resonance
- climate change
- cell proliferation
- intensive care unit
- nk cells
- low dose
- liver failure
- cell cycle
- hiv infected
- human immunodeficiency virus
- insulin resistance
- high glucose
- double blind
- contrast enhanced