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 × 10³; 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_γ) 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.