Influence of low-dose beta-interferon on natural killer cell activity in breast cancer patients subjected to chemotherapy

Abstract

The present study was designed to test whether immunomodulating doses of human beta-interferon would affect the natural cell-mediated cytotoxic function in untreated breast cancer patients or in those subjected to antitumor therapy. Analyses were performed on 11 breast cancer patients, 3 at stage 1 and 8 at stage 2, the latter being subjected to cyclophosphamide, methotrexate, 5-Fluorouracil (CMF) adjuvant chemotherapy. Five patients treated with CMF and 3 patients not subjected to adjuvant chemotherapy, received human beta-interferon (IF, 2 X 10(6) IU/patient, i.m.), on days 0,7, and 15 for 6 cycles of 31 days each. The natural killer (NK) activity (NKA) of peripheral blood mononuclear cells (MNC) was tested 24 and 48 h after low-dose IF administration. The results of NKA determinations carried out for the 6 cycles of treatment show that (1) chemotherapy alone depressed NKA; (2) IF alone increased NKA in stage 1 patients not treated with CMF; (3) IF antagonized the depressive activity of CMF on NK function and significantly augumented NKA in the case of low "basal" cytotocix activity detectable in MNC collected before IF administration. Parallel in vitro studies showed that the inhibitory effect on NKA provoked by CMF is due to cyclophosphamide present in the association and is effectively antagonized by IF. These data provide rational bases for using IF in immunochemotherapy regimens, when tumor cells are supposed to be susceptible to host control by the natural resistance function.

Comparative studies between in vitro and in vivo effects of human beta-interferon on natural killer activity and its relevance to immunochemotherapy

“…On this basis a study was designed to test whether the administration of LDIF, would affect NKA, an in vitro function possibly related to NR in vivo [6,7,11,12,16,19,20,27], in untreated breast cancer patients or in those subjected to chemotherapy according to the CMF (i.e., CTX + MTX + 5-FU) protocol. The results, reported previously [34], showed that (a) LDIF increased NKA of patients not subjected to chemotherapy; and (b) in patients treated with CMF, LDIF antagonized the depressive activity of CMF on N K function and significantly augmented NKA in those cases in which low basal activity was found at the time of LDIF administration. Parallel in vitro studies were carried out on peripheral MNC collected from cancer patients to be treated with LDIF or LDIF + CMF, to evaluate the boosting effects of [~IFN in vitro and to test whether a relationship could be found between in vivo and in vitro responses to this agent.…”