Difluoromethylornithine (DFMO) arrests murine CTL development in the late, pre-effector stage

Ancillary Activity: Beyond Core Metabolism in Immune Cells

“…The requirement for polyamines in proliferating cells indicates that this pathway is likely to be engaged during lymphocyte activation and clonal expansion. This idea is supported by numerous older reports in T cells showing a direct link between polyamine synthesis and T cell proliferation (Bowlin et al, 1987; Kay and Pegg, 1973; Schall et al, 1991; Scott et al, 1985a). In naïve T cells, the activity and production of polyamine synthesis enzymes are maintained at low levels (Kay and Lindsay, 1973; Kay and Pegg, 1973), but this changes with T cell activation as ODC and S-adenosylmethionine decarboxylase activity, the rate limiting steps in polyamine synthesis, increase within hours of stimulation (Fidelus et al, 1984; Kay and Lindsay, 1973; Kay and Pegg, 1973; Scott et al, 1985b).…”

Anticancer Drug-Induced Immunomodulation and Cancer Therapeutics

“…Again NK functions were not affected whereas in this study tumoricidal activity of macrophages against the melanoma was increased significantly, depending on time of treatment. The inhibition of CTL development by DFMO and its reversal by putrescine were confirmed by others [285]; in this study it was also found that T helper cells and accessory cells functions were not affected by the drug. In comparing the effects of DFMO with those of some derivatives, it was confirmed that DFMO augmented the effects of macrophages against B16 F 1 melanoma; a derivative was also found to exert synergistic effects with LPS or IFN on macrophages function [284]; NK functions were not affected while CTL induction was inhibited.…”

“…Indeed at low doses Cyclophosphamide inhibited the growth of murine hepatoma MH129 in immunocompetent but not in immunodepleted mice and the inhibition did not occur in mice given CD4+CD25+ T cells [166]. In this study the interesting observation was made that the administration of low dose Cyclophosphamide was more effective in causing depletion of CD4+CD25+ cells when given after tumor inoculation than when given before tumor inoculation: as the authors stated [166], this finding is of relevance to clinical Phenylalinine mustard + [147,[188][189][190][191] Busulfan + + [148,169,[192][193][194] Nitrosoureas + + [148,[195][196][197][198][199][200][201][202] Cis Platinum + + [170,203,204,205,[206][207][208][209][210][211][212][213][214][215] Difluoromethylornithine + + [280][281][282][283][284][285] trials of chemotherapy and immunotherapy combinations. In this study the interesting observation was made that the administration of low dose Cyclophosphamide was more effective in causing depletion of CD4+CD25+ cells when given after tumor inoculation than when given ...…”

Immunosuppresive Factors in Cancer

“…CTL differentiation is more affected by the inhibition of polyamine biosynthesis than CTL proliferation [304]. These data suggest that polyamines are immunostimulating for T cells.…”