Systemic administration of human leukocyte interferon to melanoma patients. III. Increased helper:suppressor cell ratios in melanoma patients during interferon treatment.
Malignant melanoma patients treated with human leukocyte interferon (IFN-alpha) displayed increased natural killer (NK) cytotoxicity to K562 targets within the first 2 weeks of therapy. This study explored the possibility of T-cell regulation of this NK response, as evidenced by a variation in T-cell subpopulations. T-cell subset levels were studied in 9 patients who received daily doses of IFN-alpha over a period of 42 days. Five monoclonal antibodies to T-cell surface markers were used: Leu 1 (pan-T), Leu 2a (T suppressor/cytotoxic), Leu 3a (T helper/inducer), HNK-1 (Leu 7, a marker for NK cells), and B73.1 (an antibody against the Fc receptor on NK/K cells). Percentages of these markers were measured on days 0, 3, 7, and 21 of treatment. Percentages of Leu 1-positive cells and Fc-receptor-positive cells remained relatively constant throughout treatment in all patients. A trend toward a decrease in suppressor cells and an increase in helper cells peaking on day 7 and returning to earlier values by day 21 was found in 5 patients. The increase in NK cytotoxicity was not reflected consistently in proportions of HNK-1-positive cells or Fc receptor-bearing cells within the first week of therapy. The most significant finding was an increase in the helper:suppressor cell ratio peaking on day 7 and returning to pretreatment values by day 21. This increase was seen in every patient studied. The average pretreatment Leu 3a:Leu 2a ratio was 0.67 increasing to an average value of 1.47 on day 7 (p less than 0.005). Leu 3a:Leu 2a ratios returned to pretreatment values, in parallel to NK activity, despite continuation of interferon therapy.
D003602:Cytotoxicity, Immunologic; D006801:Humans; D007273:Injections, Intramuscular; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D011961:Receptors, Fc / Q000032:analysis; D013601:T-Lymphocytes; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D007370:Interferon Type I; D011961:Receptors, Fc