Intratumoral Expression of Mature Human Neutrophil Peptide-1 Mediates Antitumor Immunity in Mice
Intratumoral Expression of Mature Human Neutrophil Peptide-1 Mediates Antitumor Immunity in Mice
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成熟人中性粒细胞肽-1的瘤内表达介导小鼠抗肿瘤免疫
DOI：
10.1158/1078-0432.ccr-09-0484
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发表时间：
2009-11-15
影响因子：
11.5
通讯作者：
Wei, Yu-quan
中科院分区：
文献类型：
--
作者：
Wang, Yong-sheng;Li, Dan;Wei, Yu-quan
目的：人中性粒细胞肽（HNP 1 -3）是一种小分子抗菌肽，在肿瘤内表达，与肿瘤坏死和抑制血管生成有关。最近的研究表明，HNP 1 -3可能参与宿主对肿瘤的免疫反应。实验设计：我们使用重组pSec-HNP 1，它表达一种可分泌形式的HNP 1，获得HNP 1在免疫活性小鼠的肿瘤环境中的表达，以探讨HNP 1在肿瘤免疫中的可能作用。结果：HNP 1在体外和体内均能诱导未成熟树突状细胞的活化和趋化作用。HNP 1的肿瘤内表达不仅导致显著的肿瘤生长抑制，而且增加肿瘤内的CTL浸润。脾细胞连续转移和（51）Cr释放试验显示特异性细胞免疫应答。此外，在pSec-HNP 1处理的小鼠的血清中也发现了增加的抗体，支持特异性体液免疫应答。在治疗tumors.Conclusions：这些研究结果表明，HNP 1可以发挥多种抗肿瘤作用，通过不同的机制，更重要的是，HNP 1介导的宿主免疫反应，肿瘤原位通过招募和随后的激活未成熟的树突状细胞，从而显示出良好的潜力，在癌症治疗。(Clin Cancer Res 2009;15（22）：6901-11）
Purpose: Human neutrophil peptides (HNP1-3), small molecular antimicrobial peptides, are expressed within tumors and associated with tumor necrosis and inhibition of angiogenesis. Recent investigations have suggested that HNP1-3 are likely to be involved in the host immune responses to tumors.Experimental Design: We used recombinant pSec-HNP1, which expresses a secretable form of HNP1, to obtain expression of HNP1 in the tumor milieu in immunocompetent mice to explore the possible roles of HNP1 in tumor immunity. The antitumor effects were investigated in established CT26 colon cancer and 4T1 breast cancer models.Results: HNP1-mediated chemotactic and activating effects on immature dendritic cells were detected both in vitro and in vivo. Intratumoral expression of HNP1 resulted in not only significant tumor growth inhibition but also increased CTL infiltration within tumors. Adoptive transfer of splenocytes and a (51)Cr release assay revealed specific cellular immune responses. Furthermore, increased antibodies were also found in sera from pSec-HNP1-treated mice supporting specific humoral immune responses. Increased apoptosis and decreased angiogenesis were also shown in treated tumors.Conclusions: These findings indicate that HNP1 can exert multiple antitumor effects through different mechanisms; more importantly, HNP1 mediates host immune responses to tumors in situ through the recruitment and subsequent activation of immature dendritic cells and thus shows promising potential in cancer therapy. (Clin Cancer Res 2009;15(22):6901-11)