Immunological effects of cancer chemotherapy in malignant melanoma

Summary The effects on the immune system of highdose cyclical combination chemotherapy were studied in nine patients with advanced malignant melanoma. Chemotherapy consisted of monthly cycles of dimethyl triazeno imidazole carboxamide 150 mg/m² i.v. daily from days 1–5, cyclophosphamide 1000 mg/m² i.v. on day 5, and vincristine 1.4 mg/m² i.v. on day 5.Immunological testing was carried out prior to treatment and at weekly intervals during the first month.B, T and non-B, non-T cell numbers all tended to fall early in the cycle as did the phytohaemagglutinin(PHA)-induced transformation and PHA-induced cytotoxicity to chicken red cells. Although PHA-induced transformation and cytotoxicity usually returned to normal by day 29, B and T cell numbers often remained subnormal. In contrast, levels for antibody-dependent, cell-mediated cytotoxicity (ADCC) were relatively stable throughout the cycle. Two patients with subsequent tumour response to therapy had rebound supranormal PHA transformations between weeks 1 and 3 of the first cycle. No other changes correlated with prognosis in individual patients.Analysis of the temporal relationships between PHA transformation, PHA-induced cytotoxicity, and ADCC supported the concept that the three assays reflect the function of separate mononuclear cell subpopulations.The stability of ADCC is of particular interest in view of other work suggesting that this function may be important in immune responses to tumours, including melanoma.Work was supported by grants from the National Health and Medical Research Council and the Western Australian Arthritis and Rheumatism Foundation, and the Cancer Council of Western Australia