T cell-dependent antitumor immunity mediated by secondary lymphoid tissue chemokine: augmentation of dendritic cell-based immunotherapy.
T cell-dependent antitumor immunity mediated by secondary lymphoid tissue chemokine: augmentation of dendritic cell-based immunotherapy.
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发表时间：
2001-03
期刊：
影响因子：
11.2
通讯作者：
Christopher J. Kirk;Dennis J. Hartigan-O’Connor;B. Nickoloff;Jeffrey S. Chamberlain;Martin A. Giedlin-Martin A.-Giedlin-2237376155;Lea Aukerman;James J. Mulé
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文献类型：
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作者：
Christopher J. Kirk;Dennis J. Hartigan-O’Connor;B. Nickoloff;Jeffrey S. Chamberlain;Martin A. Giedlin-Martin A.-Giedlin-2237376155;Lea Aukerman;James J. Mulé
次级淋巴组织趋化因子(SLC)是一种CC趋化因子，对幼稚T细胞和树突状细胞(DC)的募集具有选择性。在淋巴结中，SLC被认为通过将初始T细胞与DC提呈抗原共定位而在启动免疫反应中发挥重要作用。在这里，我们使用SLC作为治疗免疫原性较差的B16黑色素瘤的方法。瘤内注射SLC以CD8+T细胞依赖的方式抑制肿瘤生长。SLC诱导大量DC和T细胞进入肿瘤，这与抗肿瘤反应一致。接下来，我们使用SLC基因修饰的DC作为已建立的肿瘤的治疗方法。瘤内注射表达SLC的树突状细胞对肿瘤生长的抑制作用明显好于对照树突状细胞或单独注射SLC。用肿瘤裂解液冲击的SLC基因修饰的DC远端免疫荷瘤小鼠可引起抗肿瘤反应，而对照DC则不能。我们还发现S.C.注射表达SLC的DC可促进T细胞向免疫部位迁移。本研究表明，SLC既能诱导抗肿瘤反应，又能增强DC诱导的抗肿瘤免疫。
Secondary lymphoid tissue chemokine (SLC) is a CC chemokine that is selective in its recruitment of naive T cells and dendritic cells (DCs). In the lymph node, SLC is believed to play an important role in the initiation of an immune response by colocalizing naive T cells with DC-presenting antigen. Here, we used SLC as a treatment for tumors established from the poorly immunogenic B16 melanoma. Intratumoral injections of SLC inhibited tumor growth in a CD8+, T cell-dependent manner. SLC elicited a substantial infiltration of DCs and T cells into the tumor, coincident with the antitumor response. We next used SLC gene-modified DCs as a treatment of established tumors. Intratumoral injections of SLC-expressing DCs resulted in tumor growth inhibition that was significantly better than either control DCs or SLC alone. Distal site immunization of tumor-bearing mice with SLC gene-modified DCs pulsed with tumor lysate elicited an antitumor response whereas control DCs did not. We also found that s.c. injection of lysate-pulsed DCs expressing SLC promoted the migration of T cells to the immunization site. This report demonstrates that SLC can both induce antitumor responses and enhance the antitumor immunity elicited by DCs.