Role of natural killer and T-cells in interferon induced inhibition of spontaneous metastases of the B16F10L murine melanoma

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Abstract

We have previously demonstrated that interferon (IFN) treatment of mice bearing the spontaneously metastasizing B16F10L murine melanoma on days -5 to -1 prior to surgical removal (day 0) of the primary tumor resulted in survival of >50% of treated mice. The antitumor effect was correlated with an early increase of natural killer (NK) cell cytotoxicity followed by a later developing specific cytolytic T-cell response. The purpose of this study was to establish definitively the roles of NK, CD4, and CD8 cells as mediators of the antitumor/antimetastatic effects of IFN. Mice were depleted of NK, CD4, and/or CD8 cells during the period of IFN treatment by administration of anti-asialo-G(M1), anti-L3T4, and/or anti-Lyt-2 antisera. Depletion of NK cells, alone or in combination with T-cells, eliminated the protective effect of IFN treatment. Depletion of both CD4 and CD8 cells, however, did not significantly alter the therapeutic effect of IFN therapy. Collectively, these data conclusively demonstrated the importance of NK cells as mediators of the IFN induced antitumor state. However, in mice depleted of CD4 cells alone, the protective effect of IFN was eliminated, in spite of the presence of intact NK cells. In vitro analysis of NK cytotoxicity on day 1 after surgery demonstrated (a) a lack of IFN induced stimulation of NK activity in CD4 depleted mice and (b) a significant increase in both baseline and IFN induced NK cytotoxicity in CD8 depleted mice. These data suggested a CD8 cell mediated inhibition of NK activity/stimulation in CD4 depleted mice, possibly responsible for the lack of response to IFN therapy in that group. These results demonstrate the importance of not only individual components of the immune system but also the interaction of these components in both the natural and IFN induced control of spontaneous B16F10L metastases.

Original languageEnglish (US)
Pages (from-to)1124-1128
Number of pages5
JournalCancer Research
Volume51
Issue number4
StatePublished - 1991
Externally publishedYes

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Natural Killer T-Cells
Interferons
Melanoma
Neoplasm Metastasis
Natural Killer Cells
T-Lymphocytes
Therapeutic Uses
Group Psychotherapy
Immune Sera
Immune System

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Role of natural killer and T-cells in interferon induced inhibition of spontaneous metastases of the B16F10L murine melanoma. / Markovic, Svetomir Nenad; Murasko, D. M.

In: Cancer Research, Vol. 51, No. 4, 1991, p. 1124-1128.

Research output: Contribution to journalArticle

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