ROLE OF MACROPHAGE-COLONY-STIMULATING FACTOR IN REGULATING THE ACCUMULATION AND PHENOTYPE OF TUMOR-ASSOCIATED MACROPHAGES

In order to better define the role played by tumor-cell-derived macrop hage-colony-stimulating factor (M-CSF) in regulating the recruitment a nd phenotype of tumor-associated macrophages, Polyoma large T-transfor med fibroblastoid cell lines, derived from M-CSF-deficient osteopetrot ic op/op mice and their phenotypically normal op/+ littermate controls , were inoculated into SCID (severe combined immunodeficiency) recipie nts and both the proportion and phenotype of the macrophages present w ithin the tumors generated were determined. The results obtained indic ate that, although tumors derived from M-CSF-deficient and M-CSF-produ cing tumor cell inoculate contain a similar proportion of macrophages, the macrophages isolated from tumors lacking M-CSF appear morphologic ally less mature and express lower levels of interleukin 1 beta, tumor necrosis factor alpha and FcR gamma II mRNA. Taken together, these da ta suggest that, although M-CSF does not appear to play a critical rol e in determining the macrophage content of these tumors, it does play a role in modulating the phenotype, and potentially the functional act ivity of the macrophages present within the tumor microenvironment.