癌症在我国的发病率和致死率在逐年快速上升，严重威胁着人们的健康。目前，肿瘤免疫疗法是一种被寄予厚望的治疗手段。但是，肿瘤免疫治疗仍然面临着很多挑战，特别是免疫抑制性的肿瘤微环境。所以，寻找一种有效的手段来改善肿瘤的免疫微环境将是提高肿瘤免疫治疗效果的必由之路。我们的前期工作表明抗血管形成药物可以改善血管的功能，从而减少肿瘤的免疫抑制作用和提高免疫治疗的效果。但是，很多肿瘤对抗血管形成的药物并不敏感，本项目将利用一类可以抑制转化生长因子β和胶原蛋白形成的药物，如吡非尼酮，来研究它们对这类肿瘤中的血管和免疫细胞的作用及其分子机制，并探索吡非尼酮等与肿瘤免疫治疗联用的方案和疗效。这个研究不仅要解决肿瘤免疫治疗中的一个关键问题，也在尝试一种新的肿瘤转化医学研究模式，既从已在临床上使用的非抗癌药物中挖掘其在肿瘤治疗中的作用机制和应用价值。所以，本项目具有重要的理论研究，临床应用和社会效益三重意义。

Cancer is a leading cause of death in the world. In China, the incidence and mortality rates of cancers are increasing rapidly. Tumor immunotherapy has been considered as an ideal therapy for cancers, but it still faces many challenges. A critical one is the suppressive tumor immune microenvironment. In tumor models sensitive to anti-VEGF treatments, our previous work showed that tumor vascular normalization is an effective strategy to alleviate tumor immunosuppression and to improve the efficacy of tumor immunotherapy. In this project, we proposed to treat tumors resistant to VEGF blockers with Pirfenidone, a class of drugs which are able to suppress TGFβ signaling and reduce collagen production. We will investigate the effects and mechanisms of Pirfenidone on tumor vessels and tumor-infiltrating immune cells, and evaluate its anti-cancer effect when combined with a tumor immunotherapy. This study will not only aim to answer a critical question currently facing tumor immunology, but also try to develop a novel cancer translational study model via exploiting the potential applications of currently clinical used drugs on cancer treatments. Thus, this project may have significant impacts on basic cancer research, clinical application and social benefits.