Characterization of 3ll‐tumor variants generated by in vitro macrophage‐mediated selection

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Abstract
Following sequential interactions between activated syngeneic Mϕs and 3LL tumor cells, stable Mϕ‐resistant 3LL variants were isolated. Unlike the unselected 3LL cells, these Mϕ‐selected variants were relatively resistant to the cytostatic and cytolytic activity of activated effector Mϕs. Such Mϕ‐resistant 3LL variants evade the Mϕ tumoricidal activity by at least two mechanisms. Firstly, they manifest a reduced susceptibility towards Mϕ‐related cytotoxins such as TNF. Secondly, they actively suppress the cytotoxic potential of Mϕs through secretion of Mϕ‐inhibitory factors. The resistance of the 3LL variants to Mϕ effector cells in vitro was reflected in vivo by a higher tumorigenic and metastatic potential. No strict correlation was found between the NK sensitivity of Mϕ‐resistant and Mϕ‐sensitive 3LL cells and their metastatic ability. Hence, activated tumoricidal Mϕs may play a central role in either the elimination or selection of neoplastic cells.

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