Tumoricidal activity and cytokine secretion by tumor‐infiltrating macrophages

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Abstract
Murine macrophages from different anatomical sites were compared for their ability to become tumoricidal and to secrete interleukin‐l (IL‐I) and tumor necrosis factor (TNF) following stimulation in vitro by several biological response modifiers (BRM). Peritoneal macrophages (PM), alveolar macrophages (AM), and tumor‐infiltrating‐macrophages (TIM), isolated from B16F10 melanoma colonies in the lung, were incubated overnight with BRM [recombinant murine in‐terferon gamma (rMulFN‐γ), lipopolysaccharide (LPS), muramyl dipeptide (MDP)], either alone or in combination. PM exhibited an increased cytotoxic response following incubation with LPS or rMulFN‐γ but not with MDP. Both AM and TIM were induced to become tumoricidal following incubation with rMulFN‐γ plus LPS or rMulFN‐γ plus MDP but not after stimulation with any BRM alone; the level of cytotoxicity obtained with TIM incubated with rMulFN‐γ plus LPS was slightly lower than that observed with PM or AM, while with rMulFN‐γ plus MDP both AM and TIM had lower cytotoxicity than PM. Secretion of IL‐I and TNF was observed in PM stimulated with LPS or MDP but not with rMulFN‐γ. Likewise, secretion of IL‐I by AM or TIM was also induced with LPS, although Jess than that obtained with PM. AM stimulated with LPS secreted larger amounts of TNF than PM while TIM secreted very low amounts of TNF. However, this result may be a consequence of the enzymatic isolation procedure used to obtain TIM since TNF secretion was also impaired in LPS‐stimulated normal lung macrophages isolated by a similar enzymatic procedure, or enzyme‐treated PM. Our results suggest that TIM obtained from lung metastases share certain functional characteristics with normal AM and respond to BRM in like manner with respect to induction of tumoricidal activity and cytokine secretion.