Tanaka Kae, Jinhua Piao, Omura Ken, Azuma Miyuki
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Oral Oncol. 2007 Jul;43(6):586-92. doi: 10.1016/j.oraloncology.2006.06.009. Epub 2006 Sep 25.
We demonstrated the accumulation of CD11b(high)Gr-1(+) cells in a murine model of squamous cell carcinoma (SCC). Inoculation of NR-S1K cells derived from oral SCC induced a rapid and clear accumulation of CD11b(high)Gr-1(+) cells in secondary lymphoid organs as well as in peripheral blood. Phenotypic and morphological analyses revealed that these CD11b(high)Gr-1(+) cells were not lymphoid lineage cells, mature dendritic cells, macrophages, or granulocytes. Although the freshly isolated CD11b(high) cells lacked antigen-presenting capacity, they acquired a potent antigen-presenting capacity that included the induction of MHC class II after culture with GM-CSF and IL-4 in vitro. These results suggest that CD11b(high) cells that accumulate in tumor-bearing hosts are immature myeloid cells, but have considerable potential to differentiate into potent antigen-presenting cells under appropriate culture conditions. The use of in vitro differentiated CD11b(high) cells may be a potential strategy for obtaining patient-matched dendritic cells for tumor immunotherapy.
我们在鳞状细胞癌(SCC)小鼠模型中证实了CD11b(高)Gr-1(+)细胞的积累。接种源自口腔SCC的NR-S1K细胞可诱导次级淋巴器官以及外周血中CD11b(高)Gr-1(+)细胞迅速且明显地积累。表型和形态学分析表明,这些CD11b(高)Gr-1(+)细胞并非淋巴谱系细胞、成熟树突状细胞、巨噬细胞或粒细胞。尽管新鲜分离的CD11b(高)细胞缺乏抗原呈递能力,但在体外与GM-CSF和IL-4共同培养后,它们获得了强大的抗原呈递能力,包括诱导MHC II类分子表达。这些结果表明,在荷瘤宿主中积累的CD11b(高)细胞是未成熟的髓样细胞,但在适当的培养条件下具有分化为强大抗原呈递细胞的巨大潜力。使用体外分化的CD11b(高)细胞可能是一种为肿瘤免疫治疗获取患者匹配树突状细胞的潜在策略。