Journal of Leukocyte Biology 48:394-402 (1990) © 1990 Wiley-Liss, Inc. Down-Regulation of Macrophage I-A Expression in Tumor-Bearing Mice

During the subcutaneous growth of a highly metastatic mammary adenocarcinoma line, C3-L4 in C3H/HeJ mice, there was a rapid decline In macrophage I-A expression in vivo. The incidence of l-A macrophage subset in the spleen declined from 90 % to 10 % or less within 5 days of tumor transplantation, with a parallel decline in their absolute number. I-A expression in these cells remained suppressed for a long time until tumors became necrotic and ulcerated. In spite of a low incidence (15-20%) of I-Ak macrophages in the normal peritoneal space, tumor transplantation caused a long-lasting decline in their incidence to one-fourth of the original level. Tumor-associated macrophages were pre-dominantly I-A throughout the tumor life span. Thus I-A macrophages dominated in all anatomical compartments In tumor-bearing mice. Macrophage I-A expression was sub-stantially restored (spleen) or stimulated (peritoneal space and tumor) in tumor-trans-planted mice subjected to chronic indomethacin therapy in the drinking water, indicating a reversal of prostaglandin-mediated down-regulation of macrophage I-A expression in situ. Concomitantly, this therapy caused regression of the primary tumors and prevented lung metastasis. These results are relevant to the understanding of tumor-host interac-tions and its exploitation for immunotherapy. Key words: cancer, I-A antigen, indomethacin, PGE