Adenoviral gene transfer of stromal cell-derived factor-1 to Murine tumors induces the accumulation of dendritic cells and suppresses tumor growth
Adenoviral gene transfer of stromal cell-derived factor-1 to Murine tumors induces the accumulation of dendritic cells and suppresses tumor growth
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DOI：
10.1158/0008-5472.can-05-1493
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发表时间：
2006-04-01
期刊：
影响因子：
11.2
通讯作者：
Crystal, RG
中科院分区：
文献类型：
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作者：
Fushimi, T;O'Connor, TP;Crystal, RG
人CXC趋化因子，基质细胞衍生因子1 (SDF-1 α)，已知在体外作为淋巴细胞、单核细胞和树突状细胞的趋化因子发挥作用。在树突状细胞是强大的抗原呈递细胞的背景下，我们假设腺病毒基因转移的SDF-1 α。肿瘤可能通过吸引树突状细胞到肿瘤中来抑制原有肿瘤的生长。AdSDF-1 α在体外介导A549细胞中SDF-1 α mrna和蛋白的表达，AdSDF-1 α感染A549细胞的上清液对树突状细胞具有趋化活性。当同基因小鼠CT26结肠癌肿瘤（BALB/c）和B16黑色素瘤和Lewis肺细胞癌（C57B1/6）注射AdSDF-1 α （5 X 10(8)个斑块形成单位）时，肿瘤内均有树突状细胞和CD8（+）细胞的积累，与注射PBS或AdNull（对照载体）的肿瘤相比，肿瘤生长明显受到抑制。在肿瘤中注射AdSDF-1 α可诱导炎症增大和引流淋巴结中树突状细胞的积累。瘤内注射AdSDF-1 α可诱导肿瘤特异性ctl， AdSDF-1 α处理小鼠的脾细胞过继性转移可延长肿瘤攻击后的存活时间。有趣的是，在野生型和CD4（-/-）小鼠中却没有。在CD8（-/-）小鼠中，AdSDF-1 α抑制肿瘤的生长。这些观察结果表明，腺病毒基因转移SDF-1 α可能是在肿瘤中积累树突状细胞并引起抗肿瘤免疫反应以抑制肿瘤生长的有用策略。
The human CXC chemokine, stromal cell-derived factor 1 (SDF-1 alpha), is known to function in vitro its a chemotactic factor for lymphocytes, monocytes, and dendritic cells. In the context that dendritic cells are powerful antigen-presenting cells, we hypothesized that adenoviral gene transfer of SDF-1 alpha. to tumors might inhibit growth of preexisting tumors through attracting dendritic cells to file tumor. AdSDF-1 alpha mediated the expression of SDF-1 alpha-mRNA and protein in A549 cells in vitro, and the supernatant of the AdSDF-1 alpha-infected A549 cells showed chemotactic activity for dendritic cells. When syngeneic murine CT26 colon carcinoma tumors (BALB/c) and B16 melanoma and Lewis lung cell carcinoma (C57B1/6) were injected with AdSDF-1 alpha (5 X 10(8) plaque-forming units), there was all accumulation of dendritic cells and CD8(+) cells within the tumor and significant inhibition of tumor growth compared with tumors injected with PBS or AdNull (control vector). The injection of AdSDF-1 alpha into tumors induced the inflammatory enlargement and the accumulation of dendritic cells in the draining lymph node. Intratumoral AdSDF-1 alpha administration elicited turnor-specific CTLs and adoptive transfer of splenocytes from AdSDF-1 alpha-treated mice resulted in the elongation of survival after tumor challenge. Interestingly, in wild-type and CD4(-/-) mice but not. in CD8(-/-) mice, AdSDF-1 alpha inhibited the growth of the tumor. These observations suggest that adenoviral gene transfer of SDF-1 alpha may be a useful strategy to accumulate dendritic cells in tumors and evoke antitumor immune responses to inhibit tumor growth.