Macrophage Content of Spontaneous Metastases at Different Stages of Growth

The macrophage content of spontaneous metastases has been quantified morphometrically for a panel of rodent tumors at different stages of metastatic tumor growth. Using a histochemical technique to selectively stain macrophages, we have evaluated the relative content of macrophages in spontaneous pulmonary metastases from the 13762NF MTLn3 rat mammary adenocarcinoma and the B16-BL6 mouse melanoma, as well as in spontaneous hepatic metastases from the M5076 mouse reticulum cell sarcoma and from autochthonous reticulum cell sarcomas in SJL/J mice. Between 112 and 254 separate, individual metastases were evaluated for each of these tumors. The data show that the relative macrophage content of very small metastases is high. However, as metastases grow the relative macrophage content falls, reaching uniformly low levels by the time the metastases are 0.5 mm in diameter. These data are very similar to our previous observations on experimental metastases where the same pattern of high macrophage content in small metastases was seen. Finding the same pattern in more slowly growing, spontaneous metastases of tumors derived from several different tissues and in two species suggests that the fall in relative macrophage content is not a phenomenon isolated to experimental metastases, a particular site, or a tissue of origin for the tumor. The relative decrease in macrophage content may thus be a general phenomenon with important implications for immunotherapy directed to enhancing the tumoricidal activity of macrophages.