Myelopoiesis-associated suppressor-cell activity in mice with Lewis lung carcinoma tumors: interferon-gamma plus tumor necrosis factor-alpha synergistically reduce suppressor cell activity

Abstract

The myelopoietic stimulation which occurs in mice bearing metastatic Lewis lung carcinoma (LLC-C3) tumors is accompanied by immune suppression and the appearance of myelopoiesis-associated immune suppressor cells in the bone marrow and spleen. Low doses of recombinant murine interferon-gamma (IFN-gamma) plus recombinant human tumor necrosis factor-alpha (TNF-alpha) were used to limit myelopoiesis and, in turn, reduce the presence of myelopoiesis-associated immune suppressor cells in LLC-C3 tumor bearers. Neither IFN-gamma nor TNF-alpha alone had any effect in vitro on the growth of myeloid progenitor cells into colonies or on the suppressive activity of bone-marrow cells from LLC-C3-bearing mice. However, the combination of low doses of IFN-gamma and TNF-alpha synergistically inhibited both the growth of myeloid progenitor cells into colonies and the suppressive activity of bone-marrow cells from tumor-bearers. Similar results were obtained in vivo. When used alone, neither IFN-gamma nor TNF-alpha had any effect on myelopoiesis or on suppressor-cell activity. When combined, IFN-gamma plus TNF-alpha synergistically suppressed myelopoiesis and the presence of immune suppressive cells both in the bone marrow and in the spleen of tumor bearers. T-lymphocyte blastogenic and NK cytotoxic activities of the tumor-bearers were restored only after treatment with both IFN-gamma and TNF-alpha.