Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases

Marco Calvaruso, Michele Sommariva, Alessandra Meini, Nick Van Rooijen, Silvia Piconese, Lucia Sfondrini, Monica Tortoreto, Raffaella Bonecchi, Elda Tagliabue, Nadia Zaffaroni, Andrea Balsari, Mario P. Colombo

    Risultato della ricerca: Article

    15 Citazioni (Scopus)

    Abstract

    Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious than systemic i.p. administration against experimental lung metastases of immunogenic N202.1A mammary carcinoma cells, whereas only i.p. delivery of CpG-ODN provided anti-tumor activity, which correlated with NK cell expansion in the lung, against lung metastases of the poorly immunogenic B16 melanoma. The inefficacy of aerosol therapy to induce NK expansion was related to the presence of immunosuppressive macrophages in B16 tumor-bearing lungs, as mice depleted of these cells by clodronate treatment responded to aerosol CpG-ODN through expansion of the NK cell population and significantly reduced numbers of lung metastases. Our results indicate that tumor immunogenicity and the tumor-induced immunosuppressive environment are critical factors to the success of CpG therapy in the lung, and point to the value of routine sampling of the lung immune environment in defining an optimal immunotherapeutic strategy.
    Lingua originaleEnglish
    Numero di pagine11
    RivistaInternational Journal of Cancer
    Volume133
    Stato di pubblicazionePublished - 2013

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    Oligodeoxyribonucleotides
    Aerosols
    Neoplasm Metastasis
    Lung
    Neoplasms
    Experimental Melanomas
    Immunosuppressive Agents
    Natural Killer Cells
    Interleukin-12 Subunit p40
    Clodronic Acid
    Breast Neoplasms
    Bronchoalveolar Lavage Fluid
    Therapeutics
    Interleukin-1
    Macrophages

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

    Cita questo

    Calvaruso, M., Sommariva, M., Meini, A., Van Rooijen, N., Piconese, S., Sfondrini, L., ... Colombo, M. P. (2013). Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases. International Journal of Cancer, 133.

    Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases. / Calvaruso, Marco; Sommariva, Michele; Meini, Alessandra; Van Rooijen, Nick; Piconese, Silvia; Sfondrini, Lucia; Tortoreto, Monica; Bonecchi, Raffaella; Tagliabue, Elda; Zaffaroni, Nadia; Balsari, Andrea; Colombo, Mario P.

    In: International Journal of Cancer, Vol. 133, 2013.

    Risultato della ricerca: Article

    Calvaruso, M, Sommariva, M, Meini, A, Van Rooijen, N, Piconese, S, Sfondrini, L, Tortoreto, M, Bonecchi, R, Tagliabue, E, Zaffaroni, N, Balsari, A & Colombo, MP 2013, 'Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases', International Journal of Cancer, vol. 133.
    Calvaruso M, Sommariva M, Meini A, Van Rooijen N, Piconese S, Sfondrini L e altri. Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases. International Journal of Cancer. 2013;133.
    Calvaruso, Marco ; Sommariva, Michele ; Meini, Alessandra ; Van Rooijen, Nick ; Piconese, Silvia ; Sfondrini, Lucia ; Tortoreto, Monica ; Bonecchi, Raffaella ; Tagliabue, Elda ; Zaffaroni, Nadia ; Balsari, Andrea ; Colombo, Mario P. / Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases. In: International Journal of Cancer. 2013 ; Vol. 133.
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    abstract = "Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious than systemic i.p. administration against experimental lung metastases of immunogenic N202.1A mammary carcinoma cells, whereas only i.p. delivery of CpG-ODN provided anti-tumor activity, which correlated with NK cell expansion in the lung, against lung metastases of the poorly immunogenic B16 melanoma. The inefficacy of aerosol therapy to induce NK expansion was related to the presence of immunosuppressive macrophages in B16 tumor-bearing lungs, as mice depleted of these cells by clodronate treatment responded to aerosol CpG-ODN through expansion of the NK cell population and significantly reduced numbers of lung metastases. Our results indicate that tumor immunogenicity and the tumor-induced immunosuppressive environment are critical factors to the success of CpG therapy in the lung, and point to the value of routine sampling of the lung immune environment in defining an optimal immunotherapeutic strategy.",
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    author = "Marco Calvaruso and Michele Sommariva and Alessandra Meini and {Van Rooijen}, Nick and Silvia Piconese and Lucia Sfondrini and Monica Tortoreto and Raffaella Bonecchi and Elda Tagliabue and Nadia Zaffaroni and Andrea Balsari and Colombo, {Mario P.}",
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    AU - Calvaruso, Marco

    AU - Sommariva, Michele

    AU - Meini, Alessandra

    AU - Van Rooijen, Nick

    AU - Piconese, Silvia

    AU - Sfondrini, Lucia

    AU - Tortoreto, Monica

    AU - Bonecchi, Raffaella

    AU - Tagliabue, Elda

    AU - Zaffaroni, Nadia

    AU - Balsari, Andrea

    AU - Colombo, Mario P.

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    N2 - Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious than systemic i.p. administration against experimental lung metastases of immunogenic N202.1A mammary carcinoma cells, whereas only i.p. delivery of CpG-ODN provided anti-tumor activity, which correlated with NK cell expansion in the lung, against lung metastases of the poorly immunogenic B16 melanoma. The inefficacy of aerosol therapy to induce NK expansion was related to the presence of immunosuppressive macrophages in B16 tumor-bearing lungs, as mice depleted of these cells by clodronate treatment responded to aerosol CpG-ODN through expansion of the NK cell population and significantly reduced numbers of lung metastases. Our results indicate that tumor immunogenicity and the tumor-induced immunosuppressive environment are critical factors to the success of CpG therapy in the lung, and point to the value of routine sampling of the lung immune environment in defining an optimal immunotherapeutic strategy.

    AB - Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious than systemic i.p. administration against experimental lung metastases of immunogenic N202.1A mammary carcinoma cells, whereas only i.p. delivery of CpG-ODN provided anti-tumor activity, which correlated with NK cell expansion in the lung, against lung metastases of the poorly immunogenic B16 melanoma. The inefficacy of aerosol therapy to induce NK expansion was related to the presence of immunosuppressive macrophages in B16 tumor-bearing lungs, as mice depleted of these cells by clodronate treatment responded to aerosol CpG-ODN through expansion of the NK cell population and significantly reduced numbers of lung metastases. Our results indicate that tumor immunogenicity and the tumor-induced immunosuppressive environment are critical factors to the success of CpG therapy in the lung, and point to the value of routine sampling of the lung immune environment in defining an optimal immunotherapeutic strategy.

    KW - inflammation

    KW - lung cancer

    KW - microenvironment

    UR - http://hdl.handle.net/10447/77985

    M3 - Article

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    JO - International Journal of Cancer

    JF - International Journal of Cancer

    SN - 0020-7136

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