Modulation of formation of tumor metastases by peritoneal macrophages elicited by various agents

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Abstract
We have studied the formation of experimental B16 melanoma metastases in the lungs of mice inoculated IV with tumoricidal or nontumoricidal peritoneal macrophages elicited by various agents. IV inoculation of peritoneal Mϕ elicited by Brewer's thioglycollate medium (TG-Mϕ) 1 day before the injection of B16 melanoma cells dramatically increased the number of metastatic foci in the lungs. NIH thioglycollate broth and proteose peptone each elicited a relatively low number of Mϕ, which were morphologically distinguishable from TG-Mϕ and did not influence the yield of B16 melanoma colonies in the lungs. Resident or C. pravum-elicited Mϕ also did not augment metastatis formation. TG-Mϕ became highly tumoricidal after IP stimulation with poly I: C. However, tumoricidal TG-Mϕ inoculated IV 1 day before IV inoculation of B16 melanoma cells did not have an antimetastatic effect. On the contrary, both tumoricidal and nontumoricidal TG-Mϕ augmented metastasis formation. Poly I: C treatment had a substantial antimetastatic effect in the normal mice, but not in mice with adoptively transferred TG-Mϕ. Histological analysis revealed that IV-inoculated TG-Mϕ (tumoricidal or nontumoricidal, either viable or disrupted) induced severe intravascular reaction in the lungs, but not in the liver or kidney. This reaction manifested in the aggregation of the various blood cells, preferentially neutrophils. These reactions were not observed after IV inoculation of PMϕ or NIH TG-Mϕ. Intravascular inflammatory reactions induced by TG-Mϕ may be responsible for the augmentation of metastasis formation, partly by suppression of NK reactivity and mostly by the acceleration of the processes of tumor cell extravasation. These data may provide some insight into the failure to achieve systemic adoptive immunotherapy using activated peritoneal TG-Mϕ.