Intratumoral injection of inactivated Sendai virus particles elicits strong antitumor activity by enhancing local CXCL10 expression and systemic NK cell activation
Intratumoral injection of inactivated Sendai virus particles elicits strong antitumor activity by enhancing local CXCL10 expression and systemic NK cell activation
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DOI：
10.1007/s00262-007-0351-y
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发表时间：
2008-01-01
影响因子：
5.8
通讯作者：
Kaneda, Yasufumi
中科院分区：
文献类型：
--
作者：
Fujihara, Atsuko;Kurooka, Masayuki;Kaneda, Yasufumi
我们已经证明，灭活的，复制缺陷型仙台病毒颗粒（HVJ-E）通过产生肿瘤特异性细胞毒性T细胞和抑制调节性T细胞活性具有强大的抗肿瘤作用。在这里，我们报告HVJ-E也通过非T细胞免疫具有抗肿瘤作用。微阵列分析显示，直接注射HVJ-E诱导CXCL 10在已建立的Renca肿瘤中的表达。在HVJ-E注射后，肿瘤中的树突状细胞分泌CXCL 10。定量实时RT-PCR和免疫组织化学显示，CXCR 3+细胞（主要是NK细胞）浸润HVJ-E注射的肿瘤。此外，注射HVJ-E可引起NK细胞的全身激活，并增强其对肿瘤细胞的细胞毒性。在体内实验中，约50%的肿瘤通过HVJ-E注射根除，并且HVJ-E针对Renca肿瘤的这种活性在很大程度上通过使用抗脱唾液酸GM 1抗体的NK细胞消耗而消除。HVJ-E注射液通过增强或纠正趋化因子-趋化因子受体轴而诱导全身抗肿瘤免疫，可能成为一种潜在的肿瘤治疗新方法。
We have already demonstrated that inactivated, replication-defective Sendai virus particles (HVJ-E) have a powerful antitumor effect by both the generation of tumor-specific cytotoxic T cells and inhibition of regulatory T cell activity. Here, we report that HVJ-E also has an antitumor effect through non-T cell immunity. Microarray analysis revealed that direct injection of HVJ-E induced the expression of CXCL10 in established Renca tumors. CXCL10 was secreted by dendritic cells in the tumors after HVJ-E injection. Quantitative real-time RT-PCR and immunohistochemistry revealed that CXCR3+ cells (predominantly NK cells) infiltrated the HVJ-E-injected tumors. Moreover, HVJ-E injection caused systemic activation of NK cells and enhanced their cytotoxity against tumor cells. In an in vivo experiment, approximately 50% of tumors were eradicated by HVJ-E injection, and this activity of HVJ-E against Renca tumors was largely abolished by NK cell depletion using anti-asialo GM1 antibody. Since HVJ-E injection induced systemic antitumor immunity by enhancing or correcting the chemokine-chemokine receptor axis, it might be a potential new therapy for cancer.