Mechanism of antimetastatic immunopotentiation by low-dose cyclophosphamide

We have previously reported the antimetastatic effect of a single low-dose of cyclophosphamide (Cy) on L-TACB rat lymphoma. The phenomenon could be ad optively transferred in immunocompetent rats and is abolished in nude mice, facts for which an immunomodulatory explanation was proposed. The aim of t his paper was to identify the mechanism(s) by which spleen cells from Cy-tr eated tumour-bearing rats could exert this antimetastatic activity. Conditi oned media obtained by incubation of spleen cells from Cy-treated and non-t reated tumour-bearing rats, under specific or non-specific stimulation, wer e assayed to evaluate their effect on lymphocyte proliferation The producti on of transforming growth factor beta (TGF-P), interleukin-10 (IL-10) and n itric oxide (NO) by conditioned media was also studied. The restoration of spleen lymphoproliferative responses to normal levels when exposed to media conditioned by splenocytes from Cy-treated tumour-bearing rats, together w ith a decreased production of suppressive cytokines TGF-beta, IL-10 and NO, suggest an enhancement of host antimetastatic immunity triggered by single low-dose Cy treatment. (C) 2000 Elsevier Science Ltd. All rights reserved.