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 interferon (IFN)-alpha-2b plus interleukin-2 (IL-2) in patients with metastatic 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 phenotypic profile of T and NK cells were determined in peripheral blood mononuclear cells (PBMCs) before and after each cycle. No significant differences were found in either of the studies realized between untreated patients and their counterpart healthy controls. However, after the first cycle, there was a significant increase in NK-cytotoxic activity and in the number of CD16+/CD56+ cells that parallelled a significant decrease in the percentage of CD3+ and CD4+ lymphocytes with no changes in the proliferative response to T-cell mitogenic signals. Individual analysis of each patient on the basis of their clinical response to treatment showed that after the first cycle of immunotherapy there were no significant differences in the immunological profiles analyzed between patients with complete or partial responses and those who did not respond to treatment, whereas, at the end of the second cycle, patients who achieved complete or partial clinical responses had higher NK-cytotoxic activity that those who remained in disease progression. We conclude that subcutaneous immunotherapy with IFN-alpha-2b and IL-2 induces a systemic immunomodulatory effect on PBMCs, manifested preferentially in a systemic NK activation and expansion that is related to the clinical outcome.