Inhibition of Lymphocyte Response by Prostaglandin-producing Suppressor Cells in Patients with Melanoma

Peripheral blood mononuclear cells (PBMC) from 11 patients with metastatic melanoma (group II) had a significant decrease in blastogenesis to concanavalin A (Con A) (38.7 +/- 7.7 cpm X 10(3); mean +/- SE) compared to 21 patients who were disease free (70.6 +/- 6.7) or 16 healthy controls (83.6 +/- 10.3). If PBMC from patients were preincubated for 72 hr prior to exposure to mitogen, blastogenesis was restored to normal. In group II patients a similar improvement in reactivity of fresh PBMC occurred with indomethacin addition or following rigorous depletion of adherent monocytes. Supernatants from cells cultured with and without Con A in several group II patients contained very high levels of endogenous PGE2. Patients had a greater percentage of T lymphocytes bearing Fc receptors for ox erythrocytes (T gamma) than controls, which appeared to correlate with the increased sensitivity to suppression by exogenously added PGE2. These data suggest that the decreased blastogenesis in certain melanoma patients is due to an increase in PGE2 production by monocytes, along with an increase in lymphocyte sensitivity to its effects.