Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China.
Cancer Lett. 2010 Sep 1;295(1):17-26. doi: 10.1016/j.canlet.2010.02.009. Epub 2010 Mar 3.
We previously found that dendritic cell (DC) precursors could be recruited into the peripheral blood of B6 mice by administration of macrophage inflammatory protein (MIP)-1alpha. These MIP-1alpha-recruited DCs could induce anti-tumor protective immunity when pulsed with tumor cell lysate. In this study, MIP-1alpha-recruited DCs could not effectively suppress preestablished tumor when pulsed with B16 tumor cell lysate. However, inoculation with these DCs expressing MAGE-1 induced an anti-tumor immunity against preestablished solid and metastatic tumor from B16-MAGE-1 cells. These MIP-1alpha-recruited DCs expressed higher level of CCR7 and displayed a more significant chemotactic response toward secondary lymphoid tissue. Therefore, they are superior in the induction of cytotoxic T lymphocytes and the inhibition of tumor development and metastasis than bone marrow-derived DCs. This study established a novel approach to the treatment of preestablished solid and metastatic tumors using MIP-1alpha-recruited DCs transduced with tumor antigen gene.
我们之前发现，巨噬细胞炎性蛋白（MIP）-1α的给药可以将树突状细胞（DC）前体募集到 B6 小鼠的外周血中。这些 MIP-1α募集的 DC 在用肿瘤细胞裂解物脉冲后可以诱导抗肿瘤保护免疫。在这项研究中，用 B16 肿瘤细胞裂解物脉冲后，MIP-1α募集的 DC 不能有效抑制已建立的肿瘤。然而，接种表达 MAGE-1 的这些 DC 可诱导针对 B16-MAGE-1 细胞的已建立的实体瘤和转移性肿瘤的抗肿瘤免疫。这些 MIP-1α募集的 DC 表达更高水平的 CCR7，并对次级淋巴组织显示出更显著的趋化反应。因此，它们在诱导细胞毒性 T 淋巴细胞以及抑制肿瘤发展和转移方面优于骨髓来源的 DC。这项研究建立了一种使用转导肿瘤抗原基因的 MIP-1α募集的 DC 治疗已建立的实体瘤和转移性肿瘤的新方法。
