Immunological changes in peripheral blood mononuclear cells of patients with metastatic renal cell carcinoma after low doses of subcutaneous immunotherapy with IFN-alpha-2b and IL-2

To elucidate the immunologic changes induced by low doses of subcutaneous i nterferon (IFN)-alpha-2b plus interleukin-2 (IL-2) in patients with metasta tic renal cell cancer, we have studied a group of eight patients undergoing two cycles of immunotherapy after radical nephrectomy. Natural killer (NK) cytotoxic activity, proliferative response to T-lymphocyte mitogens, and p henotypic profile of T and NK cells were determined in peripheral blood mon onuclear cells (PBMCs) before and after each cycle. No significant differen ces were found in either of the studies realized between untreated patients and their counterpart healthy controls. However, after the first cycle, th ere was a significant increase in NK-cytotoxic activity and in the number o f CD16+/CD56+ cells that parallelled a significant decrease in the percenta ge of CD3+ and CD4+ lymphocytes with no changes in the proliferative respon se to T-cell mitogenic signals. Individual analysis of each patient on the basis of their clinical response to treatment showed that after the first c ycle of immunotherapy there were no significant differences in the immunolo gical profiles analyzed between patients with complete or partial responses and those who did not respond to treatment, whereas, at the end of the sec ond cycle, patients who achieved complete or partial clinical responses had higher NK-cytotoxic activity that those who remained in disease progressio n. We conclude that subcutaneous immunotherapy with IFN-alpha-2b and IL-2 i nduces a systemic immunomodulatory effect on PBMCs, manifested preferential ly in a systemic NK activation and expansion that is related to the clinica l outcome.