Interferon gamma and granulocyte/macrophage colony-stimulating factor inhibit growth and induce antigens characteristic of myeloid differentiation in small-cell lung cancer cell lines.

The expression of several macrophage and hemopoietic cell surface markers recently described on small-cell lung cancer (SCLC) cell lines was studied by use of flow cytometry. The antigens Leu-M3, Leu-7, and HLA-DR were examined for their modulation by human interferon gamma and granulocyte/macrophage colony-stimulating factor (GM-CSF). Both of these lymphokines generally induced enhanced expression of hemopoietic markers in several SCLC lines. A differential response to these two hormones was observed, in that qualitative and quantitative differences in marker modulation among the tested cell lines were apparent. In addition to regulating the antigenic phenotype of these cells, both interferon gamma and GM-CSF had antiproliferative effects on SCLC lines as determined by [3H]thymidine incorporation and clonal growth in agar. These results suggest that interferon gamma and GM-CSF promote a differentiation process in SCLC cell lines that has characteristics in common with myeloid differentiation. These findings support the theory that SCLC tumors are hemopoietic cells that arise from macrophages or their precursors and suggest new therapeutic modalities for the treatment of lung cancer.