LIGHT delivery to tumors by mesenchymal stem cells mobilizes an effective antitumor immune response.
LIGHT delivery to tumors by mesenchymal stem cells mobilizes an effective antitumor immune response.
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DOI：
10.1158/0008-5472.can-11-4216
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发表时间：
2012-04
期刊：
影响因子：
11.2
通讯作者：
Weibin Zou;Huilin Zheng;T. He;Jinjia Chang;yang-xin fu;W. Fan
中科院分区：
文献类型：
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作者：
Weibin Zou;Huilin Zheng;T. He;Jinjia Chang;yang-xin fu;W. Fan
骨髓来源的间充质干细胞（MSC）已被证明可以进入肿瘤组织，在那里它们促进肿瘤生长并抑制免疫排斥反应。在这项研究中，我们测试了MSC工程表达免疫刺激因子LIGHT，TNF超家族的成员，是否可以诱导肿瘤消退。利用体外和体内迁移实验，我们发现表达LIGHT的MSC（MSC-L）显示出对肿瘤组织的强烈嗜性。MSC-L处理激活了LIGHT信号通路，有效地组织了有效的抗肿瘤免疫应答，刺激了T细胞的流入并抑制了体内肿瘤生长。发现CD 4 T细胞在免疫应答的诱导阶段中起作用，并且CD 8 T细胞显示为效应阶段所必需。总之，我们的研究结果表明，MSC可以有效地归巢并将免疫刺激分子传递到肿瘤组织，从而逆转免疫抑制环境，促进抗肿瘤免疫，抑制肿瘤生长。
Bone marrow-derived mesenchymal stem cells (MSC) have been shown to home into tumor tissues, where they promote tumor growth and suppress immune rejection. In this study, we tested whether MSCs engineered to express the immune stimulating factor LIGHT, a member of the TNF superfamily, could induce tumor regression. Using in vitro and in vivo migration assays, we found that LIGHT-expressing MSCs (MSC-L) displayed a strong tropism for tumor tissues. MSC-L treatment activated the LIGHT-signaling pathway, effectively organizing a potent antitumor immune response that stimulated an influx of T cells and inhibited tumor growth in vivo. CD4 T cells were found to play a role in the induction phase of the immune response, and CD8 T cells were shown to be essential for the effector phase. Together, our findings indicate that MSCs can effectively home into and deliver immune stimulating molecules to tumor tissues, thereby reversing the immune-suppressive environment, promoting antitumor immunity, and inhibiting tumor growth.