Study of IL-2 receptor expression after chemoimmunotherapy in patients treated for metastatic malignant melanoma

Abstract

Using flow cytometry, cellular IL-2 receptors were studied before and following chemoimmunotherapy combination in 20 patients with metastatic malignant melanoma (MMM). Patients received cisplatin (100 mg/m2) at days 1 and 28, recombinant IL-2 by continuous infusion from days 3 to 6, 17 to 21, 31 to 34, and 45 to 49. Interferon-alpha (IFN-α) was given subcutaneously three times weekly. In terms of clinical response, we observed 55% objective response (complete: 15%). When pretreatment blood samples were compared with those of healthy donors, we did not observe any change in low (α chain) and high affinity receptor (α + β) expression. In contrast, intermediate affinity p75 (β chain) expression was decreased significantly (P ≤ 0.0001) in MMM patients. During treatment, we found a dramatic increase of β chain as well as high affinity (α + β) expression in responding patients, as soon as IL-2 therapy began. Furthermore, the increase of β chain expression was limited to natural killer (NK) cells (CD56+). In non-responding patients, on the other hand, increase of both receptors was seen only at day 31. These data suggest the involvement of β chain expression in the mechanism of cell activation after chemoimmunotherapy. Moreover, this early β chain expression is correlated with the clinical response to chemoimmunotherapy.