Cyclophosphamide Induces the Development of Early Myeloid Cells Suppressing Tumor Cell Growth by a Nitric Oxide-Dependent Mechanism

摘要: Adoptive immunotherapy with cyclophosphamide (Cy) increases the host resistance against tumor growth. The precise mechanism(s) by which this therapy enhances suppression is unclear. Cy induces development of early myeloid cells that may be strongly antiproliferative through NO production. These are similar to natural suppressor found in normal bone marrow a potential antitumor effect. Here we have addressed whether NO-producing involved Cy-treated mice. results show synergism between treatment and tumor-specific lymphocytes transferred systemically (i.v.) or locally (Winn's assay) strong suppression. Inhibition production N(G)-monomethyl-L-arginine at site inoculation loss protection achieved combined therapy. mice develop splenic (CD11b, Gr-1, CD31 (ER-MP12), ER-MP20, ER-MP54) producing large amounts upon T cell-derived signals (IFN-gamma plus CD40 ligation) able inhibit cell growth vitro. Early (ER-MP54(+)) expressing inducible synthase increased challenge treated therapy, but not those immune transfer alone. Thus, expansion cells, inhibiting mechanism involving NO. Both recruitment activation these appear dependent on presence lymphocytes.