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Suppression of NK-mediated natural resistance by interferon treatment of murine lymphomas

A H Greenberg, V Miller, T Jablonski

    Journal of Immunology (Baltimore, Md. : 1950)
    |April 1, 1984
    PubMed

    Insights

    Interferon (IFN) treatment reduces lymphoma's sensitivity to natural killer (NK) cells, hindering the immune system's ability to fight cancer. This effect is dependent on the presence of NK cells for tumor rejection.

    Area of Science:

    • Immunology
    • Cancer Biology
    • Virology

    Background:

    • Interferon (IFN) is known to modulate immune responses.
    • Natural killer (NK) cells play a crucial role in innate immunity against tumors.
    • Previous in vitro studies suggested IFN might affect NK cell activity.

    Purpose of the Study:

    • To investigate the in vivo effects of interferon (IFN) on the sensitivity of murine lymphomas to NK cell-mediated resistance.
    • To determine if IFN pretreatment influences tumor rejection in a dose-dependent manner.
    • To elucidate the role of NK cells in IFN-mediated modulation of tumor resistance.

    Main Methods:

    • Murine lymphomas were preincubated with IFN in vitro.
    • Tumor retention was measured in vivo using (131I)dUrd-labeled tumor cells in syngeneic and semisyngeneic mice.
    • NK cell deficiency was induced using cyclophosphamide, anti-asialo GM1 antiserum, or by using congenitally NK-deficient bg/bg mice.
    • Poly I:C was used to enhance NK-mediated resistance.

    Main Results:

    • IFN pretreatment dose-dependently suppressed natural resistance to two lymphomas in DBA/2 and BDF1 mice.
    • IFN abolished Poly I:C enhancement of NK-mediated resistance in the lung, liver, and peritoneal cavity.
    • IFN did not alter the elimination of IFN-resistant L1210R lymphoma compared to its IFN-sensitive L1210S variant.
    • In NK-deficient mice, IFN-treated and control tumors were rejected equally, indicating NK cell dependence.

    Conclusions:

    • Interferon (IFN) suppresses the sensitivity of lymphomas to NK cell-mediated host resistance in vivo.
    • The observed effects of IFN are dependent on the presence and activity of NK cells.
    • IFN pretreatment may represent a strategy to modulate tumor immune evasion, but its efficacy is linked to NK cell presence.

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