Toura I, Kawano T, Akutsu Y, Nakayama T, Ochiai T, Taniguchi M
CREST (Core Research for Evolutional Science and Technology) Project, Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Japan.
J Immunol. 1999 Sep 1;163(5):2387-91.
A unique lymphoid lineage, Valpha14 NKT cells, bearing an invariant Ag receptor encoded by Valpha14 and Jalpha281 gene segments, play crucial roles in various immune responses, including protective immunity against malignant tumors. A specific ligand of Valpha14 NKT cells is determined to be alpha-galactosylceramide (alpha-GalCer) which is presented by the CD1d molecule. Here, we report that dendritic cells (DCs) pulsed with alpha-GalCer effectively induce potent antitumor cytotoxic activity by specific activation of Valpha14 NKT cells, resulting in the inhibition of tumor metastasis in vivo. Moreover, a complete inhibition of B16 melanoma metastasis in the liver was observed when alpha-GalCer-pulsed DCs were injected even 7 days after transfer of tumor cells to syngeneic mice where small but multiple metastatic nodules were already formed. The potential utility of DCs pulsed with alpha-GalCer for tumor immunotherapy is discussed.
一种独特的淋巴细胞谱系，即Va14 NKT细胞，其携带由Va14和Ja281基因片段编码的恒定抗原受体，在各种免疫反应中发挥关键作用，包括针对恶性肿瘤的保护性免疫。已确定Va14 NKT细胞的特异性配体为α-半乳糖神经酰胺（α-GalCer），它由CD1d分子呈递。在此，我们报告用α-GalCer脉冲处理的树突状细胞（DCs）通过特异性激活Va14 NKT细胞有效诱导强大的抗肿瘤细胞毒性活性，从而在体内抑制肿瘤转移。此外，当将用α-GalCer脉冲处理的DCs注射到同基因小鼠体内时，即使在肿瘤细胞转移至已形成小的但多个转移结节的小鼠7天后，也观察到B16黑色素瘤在肝脏中的转移被完全抑制。本文讨论了用α-GalCer脉冲处理的DCs在肿瘤免疫治疗中的潜在应用。
