Macrophage content of murine sarcomas and carcinomas: associations with tumor growth parameters and tumor radiocurability

Experiments were designed to investigate whether the tumor-associated macrophage (TAM) content of murine solid tumors correlates with the clonogenic ability of tumor cells to establish s.c. tumors, tumor growth rate, extent of tumor necrosis, tumor metastatic propensity, and tumor radioresponse. Of 13 tumors studied, 6 were sarcomas and 7 were carcinomas; all tumors were of spontaneous origin in C3Hf/Kam mice, with the exception of one sarcoma that was induced by 3-methylcholanthrene. Tumors were growing in the hind thighs of syngeneic mice, and their TAM content was determined when they were 8 mm in diameter. The TAM content varied greatly among tumors, ranging from 9 to 83%. Tumor bearing mice experienced a reduction of 50% or more in the number of peritoneal macrophages, but the degree of reduction was independent of TAM content. A significant negative correlation was noted between TAM content and TD50 values (i.e., the number of tumor cells needed to produce tumors in 50% of injected sites) and between TAM content and the amount of tumor necrosis. Also, an obvious trend toward positive correlation between TAM content and reduced local tumor radiocurability was apparent. No correlation was found between TAM content and tumor growth rate or metastatic spread. TAM from the NFSA sarcoma (a tumor with a low TD50 value, almost without necrosis, and poorly responsive to radiation) stimulated the in vitro growth of NFSA tumor cells. These observations suggest that high TAM content could be conductive to tumor cell proliferation and could be a factor in poor tumor radioresponse.