SOLUBLE INTERCELLULAR-ADHESION MOLECULE-1 AND SERUM CYTOKINES IN MELANOMA PATIENTS TREATED WITH LIPOSOMES CONTAINING MURAMYL TRIPEPTIDE

Aims and background: A soluble form of intercellular adhesion molecule -1 (slCAM-1) has been recently identified in patients with malignant m elanoma. It has been demonstrated that inflammatory cytokines can modu late the cellular expression of ICAM-1 and the shedding of this molecu le by cells, To our knowledge, few data exist on serum slCAM-1 levels in cancer patients treated with immunomodulators. Liposomes containing muramyl tripeptide (MLV MTP-PE) can activate monocytes from cancer pa tients in vitro and in vive, making them cytotoxic such as tumor necro sis factor-alpha (TNF-alpha) and Interleukin-6 (11-6). The purpose of the present study was to evaluate the levels of slCAM-1 and their poss ible correlation with serum inflammatory cytokine levels in melanoma p atients treated with MLV MTP-PE. Methods: The sera from 9 patients wit h metastatic melanoma treated with MLV MTP-PE, 4 mg i.v. twice a week for 12 weeks, were tested in ELISA system to detect slCAM-1 TNF-alpha, Il-6, Interleukin-1 beta (1L-1 beta) and Interferon-gamma (IFN-gamma) before, and 2 and 24 h after the 1st, 12th and 24th infusion of MLV M TP-PE. Results: Baseline levels of slCAM-1 were elevated in ail patien ts (median 540 ng/ml: range 400-1030 ng/ml). Twenty-four h after the 1 st infusion of MLV MTP-PE, we observed 6 increases in slCAM-1 levels, 1 decrease and 2 stable values (median 720 ng/ml: range 410-1820; P = 0.060). Twenty-four h after the 12th infusion, slCAM-1 increased in 3 patients and did not change in 4 (median 790 ng/ml: range 495-1650 ng/ ml; P = 0.060). At the 24th infusion, slCAM-1 increased in 4 of 6 eval uable patients and remained stable in 2 (median 802 ng/ml: range 510-1 450 ng/ml; P = 0.045). To better analyze the variations in slCAM-1, th e patients were arbitrarily divided into two groups according to their clinical behavior: 4 presented stabilization (all lesions, n = 2; som e lesions, n = 2) (Group A); 5 presented progressive disease (Group B) . In Group A, slCAM-1 levels remained stable or showed a modest increa se during treatment (except in 1 patient, who exhibited a substantial variation after the 12th infusion). In contrast, in Group B very high levels of slCAM-1 were observed at the beginning of the study therapy in 1 patient and after the Ist infusion in 3 patients; these values re mained high until the 24th infusion. In most of the patients, TNF alph a a and 1L-6 increased after the Ist infusion, but not thereafter. IFN -gamma was never detected; IL-1 beta was detectable in a few cases, bu t only before the infusions. Conclusions baseline levels of slCAM-1 we re elevated in all patients and further increased during treatment onl y in patients with more aggres sive disease. No correlation was found between slCAM-1 and inflammatory cytokines. It would therefore seem th at in patients with advanced disease, higher levels and a progressive increase in slCAM-1 may be unfavorable prognostic factors.