"seed and soil"假说提示微环境对肿瘤转移很关键。研究显示间质干细胞（mesenchymal stem stem,MSC）可向肿瘤迁移并可转变为肿瘤相关基质细胞，从而为肿瘤转移提供合适的微环境。在前期实验里，我们将强免疫刺激因子 LIGHT转入MSC，发现MSC-L可有效控制肿瘤肺部转移灶形成，同时我们还发现MSC-L可介导抗MSC的免疫反应。在此，我们将探讨MSC-L引起的自身免疫反应与控制肿瘤转移的关系。由于MSC与肿瘤相关基质细胞如CAF、血管周细胞有极大的相似性，我们还将探寻MSC-L是否在引起抗MSC的同时激起了抗肿瘤基质细胞的免疫反应，从而破坏肿瘤赖以生存的微环境。在此基础上，我们将通过动物基因敲除模型，进一步探寻LIGHT是如何通过改变肿瘤微环境而控制肿瘤转移的。该项目的实施将有助于加深我们对免疫、肿瘤微环境与肿瘤转移的理解，从而为控制肿瘤转移提供新策略。

The 'seed and soil' hypothesis for metastasis by Paget sets forth the concept that a conducive microenvironment is required for disseminating tumor cells to engraft distant sites. Emerging evidence shows that mesenchymal stem cell (MSC) can migrate into tumor and may even transit into cancer associated fibroblasts (CAF). In addition, MSC may precede tumor cells to engraft into target organs and thereby provide pre-niche for tumor metastasis. Therefore it is reasonable that destruction of tumor niche may be an alternative strategy for tumor metastasis control. Here, our preliminary data shows that, when the potent immune stimulating factor, one of TNF superfamily members, LIGHT, tansfected into MSC, MSC-L could effectively harness tumor disseminating into lung. At the same time, we also observed that MSC-L may induce anti-MSC immunity. Thus, in this project, we would investigate whether the autoimmune against MSC itself was related with tumor metastasis control. Furthermore, due to the large resemblance between MSC, CAF and pericytes, all of which are major part of constituents of tumor stroma, we would further investigate whether the induced autoimmune response of MSC-L may also incur destruction of these tumor stroma cells, and thereby destruct the niche for tumor metastasis. Based on this, via gene knock-out mice model, we would investigate how LIGHT signaling exert an effect on tumor metastasis niche destruction. We wish that this project would benefit for us to decipher how host immunity and tumor microenvironment determine tumor metastasis, and more importantly, to shed light for us to harness tumor metastasis.