阻遏MDSCs联合γδT细胞过继免疫治疗改善抗血管生成诱导的肿瘤微环境免疫抑制的作用及机理研究

目前，抗血管生成已是常见的抗肿瘤治疗方法。然而，有研究表明，抗血管生成疗效不理想，还有增加肿瘤复发转移风险；深入分析发现，这主要涉及肿瘤微环境发生的反应性改变，尤其是MDSCs、Treg等免疫抑制细胞聚集，T细胞、NK细胞等免疫效应细胞功能障碍，造成了肿瘤微环境免疫抑制状态。最近，我们研究发现，Endostatin抗血管生成后肿瘤进展的小鼠，肿瘤组织中MDSCs增加，提示Endostatin可能通过MDSCs介导肿瘤微环境免疫抑制。为证实该假设，本项目拟在原有研究的基础上，开展Endostatin引发肿瘤微环境免疫抑制改变的研究，MDSCs在肿瘤微环境免疫抑制中重要作用的研究，进而开展阻遏MDSCs联合γδT细胞过继免疫治疗改善抗血管生成诱导的肿瘤微环境免疫抑制的作用及机理研究。这对进一步阐明肿瘤血管生长机理，肿瘤微环境免疫状态改变与肿瘤复发转移关系，拓展肿瘤治疗新思维具有开创性科学意义。

At present, the anti-angiogenic therapy has become a common anti-cancer therapy. However, accumulating evidence suggests that the anti-angiogenic therapy is not satisfactory for inhibiting tumor growth , and even has a risk of tumor recurrence and metastasis. This phenomenon is associated with a series of reactive changes that have occurred in the tumor microenvironment, especially recruiting a large number of immunosuppressive cells such as MDSCs and Treg cells, and infiltrating the T cells and NK cells with anergy. These changes resulted in the immunosuppressive state of tumor microenvironment. Our recent study have found that, the number of MDSCs increased in the tumor microenvironment after Endostatin treatment, suggesting that the anti-angiogenic therapy may induce the immunosuppressive state of tumor microenvironment. To test this hypothesis, we plan to study the changes of immunosuppressive state in tumor microenvironment induced by Endostatin ,and the important roles of MDSCs in such tumor microenvironment. Furthermore, we will explore the efficacy and mechanism of combination of blocking MDSCs with the γδT cell adoptive immunotherapy to improve the immunosuppressive state in tumor microenvironment after anti-angiogenic therapy. An foundation stone might be established by this study in the understanding of profound mechanism of tumor angiogenesis, the inevitable link between the changes of immunosuppressive state of tumor microenvironment and the tumor recurrence and metastasis. And this study might provide the new perspective expanding on cancer research and the potential clinical application of cancer therapy.