Reference - Detail
|Author||Kuroda H, Mabuchi S, Kozasa K, Yokoi E, Matsumoto Y, Komura N, Kawano M, Hashimoto K, Sawada K, Kimura T.|
|Title||PM01183 inhibits myeloid-derived suppressor cells in vitro and in vivo.|
AIM:To evaluate the ability of PM01183 to eliminate myeloid-derived suppressor cells (MDSCs).
MATERIALS & METHODS:The effect of PM01183 on MDSCs, NK cells and CD8+ T cells was examined in vitro and in vivo. The mechanism by which PM01183 depletes MDSCs was also investigated.
RESULTS:PM01183 reduced the number of MDSCs by inducing apoptosis and attenuated the MDSC-mediated suppression of CD8+ T cells by inhibiting arginase-1 production, whereas no significant effect on CD8+ T or NK cells was noted. The inhibitory effect of PM01183 on MDSC was mediated by the attenuation of STAT3 phosphorylation. The inhibitory effect of PM01183 on MDSCs was greater than those of existing anticancer agents.
CONCLUSION:PM01183 exhibits strong inhibitory effects on MDSCs.
|MeSH||Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects Arginase / metabolism CD8-Positive T-Lymphocytes / immunology* Carbolines / therapeutic use* Cell Line, Tumor Female Heterocyclic Compounds, 4 or More Rings / therapeutic use* Humans Immunosuppression Killer Cells, Natural / immunology* Lymphocyte Activation / drug effects Mice, Inbred BALB C Mice, Nude Myeloid-Derived Suppressor Cells / drug effects* Myeloid-Derived Suppressor Cells / physiology Phosphorylation STAT3 Transcription Factor / metabolism Uterine Cervical Neoplasms / drug therapy*|
|DNA material||pCAmGCSF (RDB01522) pCAZ 2 (RDB01870).|