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

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  • Eduardo Moreo

    (Universidad de Zaragoza, IIS-Aragon
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Aitor Jarit-Cabanillas

    (Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC))

  • Iñaki Robles-Vera

    (Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC))

  • Santiago Uranga

    (Universidad de Zaragoza, IIS-Aragon
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Claudia Guerrero

    (Universidad de Zaragoza, IIS-Aragon
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Ana Belén Gómez

    (Universidad de Zaragoza, IIS-Aragon
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Pablo Mata-Martínez

    (Hospital la Paz Institute for Health Research (IdiPAZ))

  • Luna Minute

    (Hospital la Paz Institute for Health Research (IdiPAZ))

  • Miguel Araujo-Voces

    (Universidad de Zaragoza, IIS-Aragon
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III
    Instituto Universitario de Oncología (IUOPA), Universidad deOviedo)

  • María José Felgueres

    (Centro Nacional de Biotecnología (CNB-CSIC))

  • Gloria Esteso

    (Centro Nacional de Biotecnología (CNB-CSIC))

  • Iratxe Uranga-Murillo

    (Universidad de Zaragoza, IIS-Aragon
    CIBER Enfermedades Infecciosas, Instituto de Salud Carlos III)

  • Maykel Arias

    (Universidad de Zaragoza, IIS-Aragon
    CIBER Enfermedades Infecciosas, Instituto de Salud Carlos III)

  • Julián Pardo

    (Universidad de Zaragoza, IIS-Aragon
    CIBER Enfermedades Infecciosas, Instituto de Salud Carlos III)

  • Carlos Martín

    (Universidad de Zaragoza, IIS-Aragon
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Mar Valés-Gómez

    (Centro Nacional de Biotecnología (CNB-CSIC))

  • Carlos Fresno

    (Hospital la Paz Institute for Health Research (IdiPAZ))

  • David Sancho

    (Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC))

  • Nacho Aguiló

    (Universidad de Zaragoza, IIS-Aragon
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

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.

Suggested Citation

  • 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 & Glo, 2023. "Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41768-8
    DOI: 10.1038/s41467-023-41768-8
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    References listed on IDEAS

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    1. Peng Liu & Liwei Zhao & Jonathan Pol & Sarah Levesque & Adriana Petrazzuolo & Christina Pfirschke & Camilla Engblom & Steffen Rickelt & Takahiro Yamazaki & Kristina Iribarren & Laura Senovilla & Lucil, 2019. "Crizotinib-induced immunogenic cell death in non-small cell lung cancer," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    2. Barbara Maier & Andrew M. Leader & Steven T. Chen & Navpreet Tung & Christie Chang & Jessica LeBerichel & Aleksey Chudnovskiy & Shrisha Maskey & Laura Walker & John P. Finnigan & Margaret E. Kirkling , 2020. "A conserved dendritic-cell regulatory program limits antitumour immunity," Nature, Nature, vol. 580(7802), pages 257-262, April.
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    1. Yin Li & Manling Jiang & Ling Aye & Li Luo & Yong Zhang & Fengkai Xu & Yongqi Wei & Dan Peng & Xiang He & Jie Gu & Xiaofang Yu & Guoping Li & Di Ge & Chunlai Lu, 2024. "UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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