Down-regulation of macrophage I-A expression in tumor-bearing mice

Abstract

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 I-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-A+ 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 predominantly 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 substantially restored (spleen) or stimulated (peritoneal space and tumor) in tumor-transplanted 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 interactions and its exploitation for immunotherapy.