In Situ Proliferation of Intratumor Macrophages

This investigation was carried out to assess whether the progressive increase in the number of macrophages associated with growing tumors was the result of an influx of monocytes from the circulation as well as proliferation of macrophages in situ. Tumor‐associated macrophages (TAM) were identified in cell suspensions prepared from three C57BL/6J (B6), methylcholanthrene‐induced sarcomas, designated MCA/76‐9, 76‐64, and 77‐23, growing in normal or irradiated mice. When the sarcomas were implanted in B6 mice exposed to a sublethal dose (800 R) of whole body irradiation (WBI), tumors grew very slowly compared with control tumors. The TAM numbers were small and the percentages of macrophages were very low. The levels of TAM corresponded with the low number of circulating blood monocytes. However, compared with the number of TAM in the initial inoculum of tumor cells injected into the WBI or control mice, the TAM numbers over a period of 14 days increased several fold in WBI mice. That this increase was initially due to infiltration from the circulation was shown by injecting macrophage‐free, cultured tumor cells into WBI or control mice. Proliferation in situ was demonstrated by autoradiography experiments. When 3 H‐thymidine was injected 1 hr before excision of MCA/76‐9 tumors, labeled cells were seen in histological sections and in cell suspensions. The labeling indices for TAM from tumors growing in WBI or normal mice were not significantly different from tumor cell labeling indices. The overall data indicated that the progressive increase in TAM in these sarcomas was the combined result of monocyte infiltration and proliferation of macrophages in situ.