Yamashita Kimihiro, Hasegawa Hiroshi, Fujita Mitsugu, Nishi Masayasu, Tanaka Tomoko, Arimoto Akira, Suzuki Satoshi, Kamigaki Takashi, Kakeji Yoshihiro
Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Anticancer Res. 2016 Jul;36(7):3659-65.
BACKGROUND/AIM: For the application of invariant natural killer T (iNKT) cells in cancer therapy, the CD40-CD40L interaction is indispensable in administering alpha-galactosylceramide (αGalCer). We hypothesized that CD40 plays an important role in dendritic cells (DC) pulsed with αGalCer (DCGs) in the treatment of lung metastases.
Wild-type (WT) and CD40(-/-) mice were treated with DCGs isolated from WT or CD40(-/-) mice in a B16F10 lung metastases model and NK and NKT cell activity in lungs and the spleen were examined.
DCG treatment improved WT mice survival but CD40(-/-) hosts received no survival benefit. Conversely, attenuation of a therapeutic effect in mice treated with CD40(-/-) DCGs was not observed. The functional activities of NK and NKT cells in DCG-treated CD40(-/-) mice were partially suppressed.
Host CD40 is essential for DCG treatment to have a therapeutic effect on B16F10 lung metastases.
背景/目的:为了将不变自然杀伤T(iNKT)细胞应用于癌症治疗,在给予α-半乳糖神经酰胺(αGalCer)时,CD40-CD40L相互作用必不可少。我们假设CD40在用αGalCer脉冲处理的树突状细胞(DC)(DCGs)治疗肺转移中起重要作用。
在B16F10肺转移模型中,用从野生型(WT)或CD40基因敲除(CD40(-/-))小鼠分离的DCGs处理野生型和CD40基因敲除小鼠,并检测肺和脾脏中的NK和NKT细胞活性。
DCG治疗提高了野生型小鼠的生存率,但CD40基因敲除宿主未获得生存益处。相反,未观察到用CD40基因敲除的DCGs处理的小鼠治疗效果减弱。DCG处理的CD40基因敲除小鼠中NK和NKT细胞的功能活性部分受到抑制。
宿主CD40对于DCG治疗对B16F10肺转移产生治疗效果至关重要。