Modulation of natural killer cell-mediated cytotoxicity by partially purified and cloned Interferon-α

Eva Lotzová, Cherylyn A. Savary, Jordan U. Gutterman, Evan M. Hersh

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

We have studied peripheral blood of 35 normal individuals, 28 solid-cancer patients, and 14 leukemic patients for natural killer (NK) cell cytotoxicity to K-562 and CEM tumor cells in a 51 Cr release cytotoxicity assay. We have found that both normal individuals and solid-cancer patients could be grouped into high (NK-HR), medium (NK-MR), and low (NK-LR) NK cell responder categories with regard to their degree of NK cell activities. However, in general, NK-HRs were found to be prevalent in normal donor population and NK-LRs in cancer patients. Leukemic patients always exhibited the NK-LR status. The difference between NK-HRs and NK-MRs appeared to be due to the relative decrease in number of active NK cells. In contrast, the NK-LR status could not be contributed to decrease of NK cells because of the dichotomy in NK cell dose-response patterns of NK-LRs versus those of NK-HRs and NK-MRs. Eighteen cancer patients undergoing interferon-a (IFN-a) therapy (3x106 units, i.m., daily) were also tested for NK cell activities after single or multiple IFN-a injections. There was a highly significant and consistent increase in NK cell cytotoxicity of patients with the NK-LR and NK-MR phenotypes following one injection of IFN-a. In contrast to the NK-LR and NK-MR group of patients, most patients displaying the NK-HR phenotype failed to show any NK cell augmentation following any number of IFN-a injections (up to 119). We have also tested NK cell activities of cancer patients undergoing treatment with low (3x106 units) and high (36 Χ 106 and 50 Χ 106 units) doses of clone A of recombinant IFN-a (IFN-arA). In these studies, all patients receiving the lower dose of IFN-arA and three of five patients receiving the higher doses of IFN-arA displayed augmented NK cell activity 24 hr after a single i.m. injection. Analysis of patients receiving the low dose of IFN-arA in a single-cell assay suggested that this agent did not modulate tumor-NK cell-binding properties but augmented significantly NK cell cytotoxicity and killing of al-ready-bound tumor targets.

Original languageEnglish (US)
Pages (from-to)2480-2488
Number of pages9
JournalCancer Research
Volume42
Issue number6
StatePublished - Jun 1 1982

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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