Role of macrophages in the immunotherapy of Lewis lung peritoneal carcinomatosis

The underlying cellular mechanisms for the antitumor effects of biological response modifiers (BRMs) have not been clearly resolved. We have investigated this issue in the Lewis lung (3LL) peritoneal carcinomatosis model in which treatment with the BRM MVE-2 slows tumor growth and enhances survival. MVE-2 is a potent inducer of cytotoxic macrophages (mφs); however, the in vivo tumoricidal properties of these mφs remain to be firmly established. To directly establish that mφs were at least in part responsible for the in vivo efficacy of MVE-2, a novel method of obtaining highly enriched mφ suspensions was developed which gave high purity, satisfactory yield, and excellent viability without affecting antitumor activity. Using the 3LL peritoneal carcinomatosis model and adoptive transfer techniques, we directly demonstrate that the majority of antitumor activity was associated with the adherent cell fraction enriched for mφs. Histological observations supported this conclusion, indicating that MVE-2 treatment initially activated cells associated with nonspecific immunity, retarding tumor growth in the ascites long enough for a multifaceted immune response to develop. J. Leukoc. Biol. 56: 41–51; 1994.