Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells
Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells
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DOI：
10.1002/eji.200526042
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发表时间：
2005-05
影响因子：
5.4
通讯作者：
H. Xin;T. Kikuchi;S. Andarini;S. Ohkouchi;Takuji Suzuki;T. Nukiwa;Huqun;K. Hagiwara;T. Honjo;Y. Saijo
中科院分区：
文献类型：
--
作者：
H. Xin;T. Kikuchi;S. Andarini;S. Ohkouchi;Takuji Suzuki;T. Nukiwa;Huqun;K. Hagiwara;T. Honjo;Y. Saijo
CX 3C趋化因子fractalkine（CX 3CL 1）以促进牢固细胞粘附的膜结合形式和表达其受体CX 3CR 1的可溶性形式存在。当将表达小鼠fractalkine的腺病毒载体（AdFKN）转导至肿瘤细胞时，fractalkine在体外以肿瘤细胞上的膜结合形式和上清液中的可溶形式表达。肿瘤内注射AdFKN（1× 109 PFU/肿瘤）至C26和B16 F10肿瘤中导致与对照相比肿瘤生长显著减少（C26：86.5%，p<0.001; B16 F10：85.5%，p<0.001）。肿瘤组织的组织学检查显示用AdFKN治疗后3天和/或6天大量NK细胞、树突状细胞和CD 8 + T淋巴细胞浸润。来自经AdFKN处理的小鼠的脾细胞产生肿瘤特异性细胞毒性T细胞，从而免受亲本肿瘤细胞的再攻击。AdFKN的抗肿瘤作用在NK细胞耗竭小鼠和CD 8-/-小鼠中完全消除，在CD 4-/-小鼠中部分阻断。这些数据表明，fractalkine通过NK细胞依赖性和T细胞依赖性机制介导抗肿瘤作用。该研究表明，Fractalkine可以作为肿瘤免疫基因治疗的合适候选者，因为Fractalkine可以诱导先天性和适应性免疫。
The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane‐bound form promoting firm cell‐cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane‐bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1×109PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8+ T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor‐specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell‐depleted mice and CD8–/– mice, and partially blocked in CD4–/– mice. These data indicated that fractalkine mediates antitumor effects by both NK cell‐dependent and T cell‐dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity.