TUMOR-CELL VACCINES THAT SECRETE INTERLEUKIN-2 (IL-2) AND INTERFERON-GAMMA (IFN-GAMMA) ARE RECOGNIZED BY T-CELLS WHILE RESISTING DESTRUCTION BY NATURAL-KILLER (NK) CELLS

The inoculation into mice of genetically engineered tumour cells that secrete IL-2 or IFN gamma results in rejection, while unmodified paren tal tumour cells grow progressively. In vivo studies demonstrated syne rgy between IL-2 and IFN gamma leading to the rejection of the transdu ced tumour cells. IL-2 is required for T cell proliferation and differ entiation. IFN gamma induced the upregulation of MHC class I molecules that present peptides to CD8(+) T cells. Furthermore, IFN gamma can c orrect defects in antigen processing. Thus, for T cells, IL-2/IFN gamm a-secreting double cytokine tumour cell vaccines might serve as class I+ peptide/antigen presenting depots for developing effector cells. In contrast to T cells, NK cells exert spontaneous killing and kill clas s I+ targets less well than those that are class I-. For this reason, they may actually have a detrimental effect by destroying a class I+ t umour cell vaccine before adequate T cell stimulation occurs. Based up on this rationale, we tested the hypothesis that an unrecognised benef it of increased class I expression by tumour cells in response to IFN gamma secretion would be to enable cytokine-secreting vaccine cells to resist destruction by NK cells. Our results demonstrated that T cells recognised tumour cells secreting IFN gamma better than those secreti ng IL-2. NK cells, in contrast, were inhibited by tumour cells that se creted IFN gamma, but not by those that secreted IL-2. The findings su ggest that, in addition to upregulating adhesion molecules, MHC molecu les, and correcting defects in antigen presentation pathways, IFN gamm a secretion may protect tumour cell vaccines from early NK-mediated de struction, keeping them available for T cell priming. Copyright (C) 19 96 EIsevier Science Ltd