Journal Article

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

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

2023

Overview

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. Intravesical administration of BCG is a standard treatment for bladder cancer. In this study, the authors examine the effect of systemic BCG administration in murine models of primary lung cancer and melanoma metastasis, demonstrating a beneficial effect either alone or in combination with PD-L1.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/31 / 631/67/1059/2325 / 64/60 / 692/699/67/1059/2325 / Acute toxicity / Adenocarcinoma / Animal models / Bacillus Calmette-Guerin vaccine / BCG / Bladder / Bladder cancer / CD8 antigen / Cell-mediated immunity / Dendritic cells / Humanities and Social Sciences / Immune checkpoint inhibitors / Immune response / Immunity / Immunotherapy / Inoculation / Intravenous administration / Lung cancer / Lymphocytes / Lymphocytes T / Melanoma / Metastases / Metastasis / multidisciplinary / Natural killer cells / PD-L1 protein / Science / Science (multidisciplinary) / Tumors