肿瘤免疫治疗的新近进展为人类战胜恶性肿瘤带来了希望，但仍面临着一些严峻的挑战，如反应率低和缺乏可靠的疗效评估手段。我们的前期研究发现：免疫检查点疗法可诱导肿瘤血管正常化，且正常化的程度与其疗效呈正相关。据此，我们提出科学假说：肿瘤血管功能的影像学信号可转化为对肿瘤浸润免疫细胞活性的实时监测，并用于建立新型的序贯性肿瘤免疫联合治疗。为此，我们将在结肠癌病人中验证免疫检查点疗法可诱导肿瘤血管正常化；通过阐明免疫检查点疗法对肿瘤血管的作用机制，建立关键免疫效应成份，如CD8+ T细胞、IFNγ、CXCL9，与肿瘤血管功能的可视化关联；然后在对免疫检查点疗法耐受的肿瘤模型，探索基于实时监测T细胞活性的新型高效的序贯性免疫联合治疗方案。本项目的顺利完成将建立一种全新的基于肿瘤血管功能的可视化监测肿瘤浸润免疫细胞活性的方法，并为构建新型的肿瘤精准免疫治疗策略提供理论依据，造福癌症患者。

Cancer immunotherapy has brought a hope to cure malignant cancers, but only in a small fraction of cancer patients. Low response rates and lack reliable approaches to evaluate and predict the therapeutic efficacy, represent two major challenges currently facing immune checkpoint blockade therapy (ICB). Our recent studies found that ICB induces tumor vascular normalization and the increased vessel perfusion positively correlates with its therapeutic efficacy. Thus, we hypothesized that the function status of tumor blood vessels can be served as a novel visible biomarker to predict the activities of tumor-infiltrating immune cells stimulated by ICB. To test this hypothesis, we will confirm that ICB can induce tumor vascular normalization in colon cancer patients. Second, we will investigate the molecular mechanism mediated the effects of ICB on the formation and function of tumor blood vessels, and then analyze the dynamic relationship between the function status of tumor blood vessels and key tumor-infiltrating immune effectors, including CD8+ T cells, IFNγ, and CXCL9. Finally, we will explore rationally scheduled combinational ICB to overcome the resistance of a tumor to ICB. The successful completion of this project may identify a novel biomarker to authentically reflect the activities of tumor-infiltrating immune effector cells according to tumor vessel function, and establish a new strategy to realize precision cancer immunotherapy based on noninvasive biomarkers. These findings may guide to develop more potent combinational cancer immunotherapy in the clinic and bring long-term survival benefits to more patients suffering from cancers.