[Correlation between functional capability and phenotypic characteristics of peripheral blood lymphocytes in patients...

Malignant melanoma is well known for its poor response to chemotherapy, radiotherapy and its susceptibility to immunotherapy. Considering that dacarbazine (DTIC) and interferon alpha (IFNalpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFNalpha monotherapy, as well as with their combination in metastatic disease. Pre-therapy values of immunological parameters showed significantly decreased NK cell activity, altered in vitro production of TNFalpha, IL-2 and proliferative response of peripheral blood lymphocytes (PBL), while percentage of PBL subpopulations was unchanged. During therapy, NK cell activity was significantly increased after the 1st cycle of combined chemoimmunotherapy (DTIC + IFNalpha), followed by a significant decrease after the 2nd cycle of therapy. Furthermore, in this group, there was a significant increase in CD4+ T helper cell percentage after the 1st cycle of therapy. Serial monitoring of activation antigens also showed a significant increase in the expression of CD38 on CD8+ cytotoxic T cells, after the 1st and 2nd cycle in combined chemoimmunotherapy group and, after 30 days, in the group of patients treated with IFNalpha, only. The increase in the expression of HLA-DR activation antigen on CD3+ and CD8+ T cells had a gradual increase and significant rise after the 2nd cycle of combine chemoimmunotherapy, only. The dynamic of immunological changes, mostly observed in combined chemoimmunotherapy, and rarely in IFNalpha monotherapy gives valuable insight into induced immunomodulation, suggesting early, but transient favourable changes, that could be prolonged by timely introduction of other immunotherapeutic agents.