Differential induction of suppressor macrophages by cloned Lewis lung carcinoma variants in mice.
The splenic T-lymphocyte blastogenic and natural killer cell (NK) activities of C57BL/6 mice bearing cloned metastatic C3 or nonmetastatic C8 variants of the Lewis lung carcinoma were suppressed. The suppression was greater in mice bearing the metastatic C3 tumors than the nonmetastatic C8 tumors, although primary tumor sizes were similar. Macrophages were shown to cause this differential in immune responsiveness, while depletion of splenic macrophages by adherence restored the T-cell and NK responses. Also, splenic macrophages from C3 tumor bearers were more suppressive to normal spleen cell activities than were splenic macrophages from C8 tumor bearers. The suppression by the macrophages of C3 bearers was indomethacin sensitive and was associated with an increased secretion of prostaglandin E2 (PGE2). Normal macrophages incubated with C3 culture supernatants were more suppressive to NK and T-cell activities and secreted more PGE2 than did macrophages incubated with the C8 supernatants or with medium. This finding suggested that the immune suppression in mice bearing C3 tumors was initiated by a soluble tumor factor(s) that stimulated the development of prostaglandin-dependent suppressor macrophages. An in vivo study examined if treating C3-bearing mice with indomethacin to prevent the prostaglandin-dependent macrophage suppressor activity would influence host survival. The survival time of C3-bearing mice treated with indomethacin was prolonged. These results suggest that the macrophage-mediated immune suppression induced by tumor cells may facilitate tumor growth and metastasis.
D000818:Animals; D002478:Cells, Cultured; D002999:Clone Cells; D015232:Dinoprostone; D005260:Female; D007108:Immune Tolerance; D007213:Indomethacin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011458:Prostaglandins E / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D011458:Prostaglandins E; D015232:Dinoprostone; D007213:Indomethacin