结直肠癌（CRC）具有较高的转移率和复发率，是最常见的恶性肿瘤之一。近年来，肿瘤微环境及免疫逃逸在CRC发生发展中的作用越来越受关注。研究表明，间充质干细胞（MSCs）是抑制性免疫微环境形成的罪魁祸首，可抑制T细胞介导的肿瘤特异性免疫，而肿瘤微环境作用下MSCs对NK细胞活化及功能的影响仍未阐明。项目组前期研究发现，肿瘤微环境作用下的MSCs会诱导NK细胞表达激活性受体NKG2D的配体MICA/MICB，并脱落形成可溶性sMICA/MICB，为自身及肿瘤细胞提供了免遭NK细胞杀伤的“保护伞”。因此，本项目聚焦在肿瘤微环境作用下，MSCs在重编程的同时通过脱落自身MICA/MICB分子，形成抑制NK细胞活化和功能的免疫抑制微环境，从体内和体外系统研究CRC肿瘤微环境作用下MSCs对NK细胞活化和功能的调控及机制。藉此为建立NK细胞抗肿瘤效应的肿瘤免疫治疗提供实验依据和理论基础。

Colorectal cancer has the high tendency to metastasis and relapse. Recently, Conceptual progress has added two emerging hallmarks of potential generality to this list—tumor microenvironment and evading immune destruction. More and more studies demonstrated that MSCs were the main culprit to construct the suppression of the immune microenvironment of tumor, focusing the regulatory function of MSCs on T cells. However, the regulatory function of MSCs on NK cells has been unknown, which is another of key killer cells for tumor immunity. Our previous study found that MICA/ MICB were induced on MSCs by simulation of the tumor microenvironment such as hypoxia, chemotherapeutic drug, and CRC cells. And, MICA/ MICB shed from the surface of MSCs to protect tumor-associated MSCs and tumor cells from NK cell killing. So, our study will focus on the interaction and mechanisms of MSCs with NK cells in tumor microenvironment to find the new strategy of tumor immunotherapy based on NK cells.