Enhancement of anti‐tumor immunity by tumor cells transfected with the secondary lymphoid tissue chemokine EBI‐1‐ligand chemokine and stromal cell–derived factor‐1αchemokine genes
Enhancement of anti‐tumor immunity by tumor cells transfected with the secondary lymphoid tissue chemokine EBI‐1‐ligand chemokine and stromal cell–derived factor‐1αchemokine genes
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DOI：
10.1002/1097-0215(200002)9999:9999
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发表时间：
2001-03
影响因子：
6.4
通讯作者：
Tetsuhiko Nomura;H. Hasegawa;Masashi Kohno;Miho Sasaki;S. Fujita
中科院分区：
文献类型：
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作者：
Tetsuhiko Nomura;H. Hasegawa;Masashi Kohno;Miho Sasaki;S. Fujita
一些新的淋巴细胞特异性趋化因子已被分离出来，这些趋化因子可吸引幼稚T细胞和记忆T细胞、B细胞、树突状细胞和自然杀伤细胞。我们已经在小鼠模型（甲A纤维肉瘤和HM - 1卵巢肿瘤）中发现了3种主要淋巴细胞特异性趋化因子，次生淋巴组织趋化因子（SLC）， EBI - 1配体趋化因子（ELC）和基质细胞衍生因子(SDF) - 1α的抗肿瘤作用的证据。在初始和免疫小鼠中，与对照肿瘤相比，表达SLC、ELC或SDF‐1α的肿瘤表现出延迟的进展。在用表达这3种趋化因子基因中的1种的肿瘤细胞免疫的小鼠中，与对照小鼠相比，用亲代肿瘤细胞攻击导致的进展略慢，而在用转染IL - 2或粒细胞-巨噬细胞集落刺激因子（GM - CSF）以及这些趋化因子的肿瘤细胞免疫的小鼠中，所有肿瘤都消退了。此外，用这些“双转染”肿瘤细胞免疫的小鼠脾脏细胞对亲代肿瘤细胞表现出更高的增殖反应和更强的细胞毒性活性。这些抗肿瘤作用与肿瘤和局部淋巴结内白细胞群的深刻改变有关，这是由于I型T细胞依赖性反应的激活，产生高水平的IFN - γ。这些发现表明，SLC、ELC和SDF - 1α可以增强全身和局部的抗肿瘤免疫，这些趋化因子可能在临床上有用，特别是当与IL - 2和GM - CSF联合使用时。©2001 Wiley‐Liss, Inc。
Several new lymphocyte‐specific chemokines, which attract naive and memory T cells, B cells, dendritic cells and natural killer cells, have been isolated. We have found evidence of the anti‐tumor effects of 3 major lymphocyte‐specific chemokines, secondary lymphoid tissue chemokine (SLC), EBI‐1‐ligand chemokine (ELC) and stromal cell–derived factor (SDF)‐1α, in murine models (Meth A fibrosarcoma and HM‐1 ovarian tumor). In both naive and immunized mice, tumors expressing SLC, ELC or SDF‐1α showed delayed progression compared with control tumors. In mice immunized with tumor cells expressing 1 of these 3 chemokine genes, challenge with parental tumor cells resulted in slightly slower progression than in control mice, while in mice immunized with tumor cells transfected to co‐express IL‐2 or granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) as well as these chemokines, all tumors regressed. Furthermore, spleen cells from mice immunized with these “double‐transfected” tumor cells exhibited higher proliferative responses and greater cytotoxic activity against parental tumor cells. These anti‐tumor effects were associated with profound alterations in the leukocyte populations within the tumors and regional lymph nodes, and this was due to activation of type I T cell‐dependent responses that produced high levels of IFN‐γ. These findings show that SLC, ELC and SDF‐1α enhance anti‐tumor immunity both systemically and locally and that these chemokines may be clinically useful, especially when combined with IL‐2 and GM‐CSF. © 2001 Wiley‐Liss, Inc.