Development of new anti-cancer therapy and anti-liver cirrhosis treatment using by NKT cells activated withα-Galcer.

我们报道了NKT细胞在癌变状态下的低反应性。在动物模型中，CD11b+ Gr1+细胞在患癌状态下增加，产生一氧化氮，抑制NKT细胞功能。我们也报道了反式维甲酸（ATRA）可以消除NKT细胞在癌变状态下的低反应性。我们在本研究中明确表明，动物模型中的CD11b+ Gr1+细胞在人类模型中是CD33+ CD14- CD11b+细胞，该群体抑制了癌症患者的NKT细胞功能。我们还指出，ATRA能够在体外消除癌症患者NKT细胞的低反应性。肿瘤患者CD11b+ Gr1+细胞中VEGF的表达高于健康供者，而FOXP3的表达在肿瘤患者和健康供者之间无显著差异。使用抗VEGF抗体治疗肿瘤后，有CD33+ CD14- CD11b+细胞减少的趋势。基于本研究结果，我们提示抗VEGF抗体可能具有减轻癌症患者免疫抑制的能力，而抗VEGF抗体已被用作癌症治疗药物。我们相信这一结果将成为使用NKT细胞进行新的癌症治疗的重要基础研究，我们可以将这种治疗方法用于从结直肠癌开始的几种癌症治疗。

We reported hypo responsiveness of NKT cells in cancer-bearing state. In animal models, CD11b+ Gr1+ cells are increased in cancer-bearing state, which produce nitric oxide and suppress NKT cell functions. We reported also all trans retinoic acid (ATRA) can absolve hypo responsiveness of NKT cells in cancer-bearing state. We showed clearly in this study that CD11b+ Gr1+ cells in animal models were CD33+ CD14- CD11b+ cells in human, and this population suppressed NKT cell functions in cancer patients. We also indicated that ATRA is able to absolve hypo responsiveness of NKT cells in cancer patients in vitro. CD11b+ Gr1+ cells which increased in cancer patients more expressed VEGF than in healthy donors, but FOXP3 expressions were no significant difference between cancer patient and healthy donors. There was a trend toward that CD33+ CD14- CD11b+ cells were reduced after cancer therapy using with anti VEGF antibody. Based on the result of this study, we indicate that anti VEGF antibody which is already used as cancer therapy drug could be have ability of reducing immune suppression in cancer patient. We believe that this result will be important basic study for new cancer therapy using with NKT cells and we can use this treatment for several cancer therapy commencing with colorectal cancer.