Influence of PGE on the immune response in melanoma-bearing mice.

This study was performed to correlate the role of exogenous and endogenous prostaglandins on humoral and cellular immune responses to and rate of growth of B-16 melanoma in vivo. B-16 melanomas synthesized 7 times as much PGE as did adjacent normal tissues, an effect that was abolished by indomethacin. In C57BL/6J mice bearing B-16 melanomas splenic plaque-forming cells, hemagglutinin titers, and delayed hypersensitivity (all to SRBC) were profoundly suppressed; these responses were significantly augmented by treating the mice with di-M-PGE2 (16, 16-dimethyl-PGE2-methyl ester), a long acting analogue of PGE2, and either further suppressed or unaffected by indomethacin, a potent inhibitor of endogenous PGE biosynthesis. Compared to control experiments, indomethacin hastened the rate of development of palpable subcutaneous B-16 tumors and facilitated the proliferation of these cells in solid tumors as well as in ascites. Pretreatment of mice with di-M-PGE2 (before inoculation with tumor cells) resulted in delay in the rate of appearance of tumors, decline in the growth rate, and increased survival. These data suggest that prostaglandins are involved in the control of in vivo tumor cell growth largely by virtue of their effects on the immune response.