Inhibition of suppressor-cell activity by cyclophosphamide in patients with malignant melanoma
Twenty patients with malignant melanoma were treated with cyclophosphamide (100, 300 or 500 mg/m2 i.v.) in pilot studies to determine whether such treatment affected suppressor-cell activity. Delayed hypersensitivity to dinitrochlorobenzene and other recall antigens, the serological response to primary immunization with pneumococcal or influenza virus antigens, and the serological response to melanoma antigens were found to be normal and were not changed by cyclophosphamide (Cy) treatment. In vitro assays for production of antibodies against sheep red blood cell (SRBC) antigens, reactivity in the mixed lymphocyte culture reaction, and induction of suppressor cells by Concanavalin-A (Con-A) yielded abnormal results as a consequence of increased suppressor-cell activity in eleven, three, and nine patients, but no concordance was seen between results with the three assays prior to treatment. After treatment with Cy, the results of these tests became normal in seven, three, and seven of the patients with previously abnormal results, independent of the dose given. Examining all patients as a group, a statistically significant effect was seen after treatment with Cy on days 14 and 21 in the assay for the production of antibodies against SRBC, and days 7, 14, 21, 28, and 35 in the assay for Con-A-induced suppressor cells. The decrease in suppressor-cell activity was largely restricted to patients who showed increased suppressor-cell activity prior to treatment with Cy. Our results suggest that increased suppressor-cell activity in patients with malignant melanoma does not affect immune reactions generally but is selective, and that the anti-suppressor-cell effect of Cy is restricted to reactions with increased suppressor-cell activity to start. Based on these results, attempts at increasing the immune response to melanoma antigen vaccines administered between 7 and 35 days after treatment with Cy seem justified.