Kuroda Hiromasa, Mabuchi Seiji, Kozasa Katsumi, Yokoi Eriko, Matsumoto Yuri, Komura Naoko, Kawano Mahiru, Hashimoto Kae, Sawada Kenjiro, Kimura Tadashi
Department of Obstetrics & Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Laboratory of Biochemistry & Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
Immunotherapy. 2017 Sep;9(10):805-817. doi: 10.2217/imt-2017-0046.
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.
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.
PM01183 exhibits strong inhibitory effects on MDSCs.
评估PM01183清除髓源性抑制细胞（MDSCs）的能力。
在体外和体内检测PM01183对MDSCs、自然杀伤细胞（NK细胞）和CD8 + T细胞的作用。同时也研究了PM01183消耗MDSCs的机制。
PM01183通过诱导凋亡减少MDSCs数量，并通过抑制精氨酸酶-1的产生减弱MDSC介导的对CD8 + T细胞的抑制作用，而对CD8 + T细胞或NK细胞无显著影响。PM01183对MDSC的抑制作用是通过减弱信号转导和转录激活因子3（STAT3）的磷酸化介导的。PM01183对MDSCs的抑制作用大于现有抗癌药物。
PM01183对MDSCs具有强大的抑制作用。
