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Role of Natural Killer Cells in the Mechanism of the Antitumor Effect of Interferon on Moloney Sarcoma Virus-transformed Cells¹

Department of Microbiology and Immunology, The Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129

The growth of tumors induced by inoculation of cells transformed by Moloney sarcoma virus can be inhibited by in situ administration of interferon (IFN) beginning one day after tumor challenge and continuing for 2 or 3 additional days. Inhibition of tumor growth by IFN was associated with a marked augmentation of natural killer (NK) cell activity, both in the spleen and at the site of tumor challenge, by day 5 after tumor challenge. However, using optimal conditions for IFN treatment, depletion of NK cells by in vivo treatment with anti-asialo GM1 prior to tumor challenge had no significant effect on inhibition of tumor growth by IFN. When the tumor load was greater or when IFN treatment was shorter, treatment with anti-asialo-GM1 partially abrogated the inhibition of tumor growth by IFN. In vitro assays gave no evidence of IFN enhancement of specific T-cell or activated macrophage antitumor effect. These results suggest that under optimal treatment conditions, the mechanism of the antitumor effect of IFN was independent of augmentation of NK activity, but under suboptimal conditions NK cells play a role in the mechanism of the antitumor effect of IFN.

¹ This work was supported by grant AI-16840 from the NIH and grant IN-125-C from the American Cancer Society.

² Recipient of a fellowship from the Samuel Roberts Noble Foundation. Present address: Department of Microbiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033.

³ To whom requests for reprints should be addressed.

Received 3/28/85. Revised 7/26/85. Accepted 9/19/85.

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