Gao Jian-Qing, Tsuda Yasuhiro, Han Min, Xu Dong-Hang, Kanagawa Naoko, Hatanaka Yutaka, Tani Yoichi, Mizuguchi Hiroyuki, Tsutsumi Yasuo, Mayumi Tadanori, Okada Naoki, Nakagawa Shinsaku
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China.
Cancer Immunol Immunother. 2009 Feb;58(2):291-9. doi: 10.1007/s00262-008-0554-x. Epub 2008 Jul 16.
Natural killer (NK) cells have been demonstrated could play an important role in the treatment of a number of tumors in mice. In the present study, chemokine CCL27, which be considered only selectively chemoattracts cutaneous lymphocyte antigen positive memory T cells and Langerhans cells, firstly demonstrated that it could induce the accumulation of NK cells into tumor by the intratumoral injection of CCL27-encoding fiber-mutant vector, AdRGD-CCL27. Experiments using spleen cell fractionation and RT-PCR showed CCL27 receptor, mCCR10, was strongly expressed in NK cells, suggesting the accumulation of NK cells in tumor was attributed to chemoattractant activity of CCL27 itself. Moreover, the combination of AdRGD-CCL27 and AdRGD-IL-12 induced the synergistic anti-tumor activity via NK-dependent manner and induced more NK cells infiltration into tumor nodule than that induced by AdRGD-CCL27 alone or AdRGD-IL-12 alone.
自然杀伤（NK）细胞已被证明在小鼠多种肿瘤的治疗中可发挥重要作用。在本研究中，趋化因子CCL27以往仅被认为可选择性趋化皮肤淋巴细胞抗原阳性记忆T细胞和朗格汉斯细胞，而通过瘤内注射编码CCL27的纤维突变载体AdRGD-CCL27，首次证明其可诱导NK细胞在肿瘤中聚集。利用脾细胞分级分离和逆转录聚合酶链反应（RT-PCR）进行的实验表明，CCL27受体mCCR10在NK细胞中强烈表达，这表明肿瘤中NK细胞的聚集归因于CCL27自身的趋化活性。此外，AdRGD-CCL27与AdRGD-IL-12联合使用通过NK依赖的方式诱导了协同抗肿瘤活性，并且与单独使用AdRGD-CCL27或AdRGD-IL-12相比，诱导了更多NK细胞浸润到肿瘤结节中。
