乏氧是促进肿瘤免疫逃逸的重要因素，精准量化乏氧微环境下PD-L1的表达状态是临床免疫治疗的迫切需求，目前缺乏合适的手段。申请人前期研究发现，乏氧微环境下诱导生成的HIF-1α可以促进结直肠癌PD-L1的表达。18F-FMISO的摄取可精准量化HIF-1α的表达水平，并与结直肠癌 PD-L1的表达呈正相关，提示18F-FMISO PET显像可成为监测乏氧调控PD-L1表达演变的有效手段。基于以上研究基础，本项目拟从细胞和动物水平结合分子生物学方法揭示乏氧调控结直肠癌PD-L1表达演变的分子机制及演变规律；通过Micro-PET显像探讨乏氧微环境下PD-L1表达与18F-FMISO摄取的内在关系，获得量化PD-L1表达的影像特征；进一步明确18F-FMISO PET定量评估靶向PD-1/PD-L1治疗效果的可行性及有效性，为临床高效、便捷筛选结直肠癌免疫治疗获益人群及疗效评价提供新策略。

Hypoxia is an important factor to promote tumor immune escape. Accurate quantification of the PD-L1 expression in the hypoxic microenvironment is an urgent need for clinical immunotherapy. Up to now, there is no suitable methods. Our previous research demonstrated that HIF-1α which was induced by hypoxic microenvironment can promote the expression of PD-L1 in colorectal cancer. The uptake of 18F-FMISO can accurately quantify the expression level of HIF-1α, and positively correlated with the expression of PD-L1 in colorectal cancer, suggesting that 18F-FMISO PET imaging may be an effective method to evaluate PD-L1 expression which regulated by hypoxia. Based on our previous research basis, the objective of this study is to reveal the molecular mechanism and evolution rules of hypoxia-regulated the expression of PD-L1 in colorectal cancer at the cellular and animal levels combined with molecular biology methods. We used Micro-PET imaging to explore the internal relationship between PD-L1 expression and 18F-FMISO uptake in a hypoxic microenvironment, in order to obtain image features of quantifying PD-L1 expression. We further verify the feasibility and availability of 18F-FMISO PET in quantitative assessment the therapeutic effect of targeted PD-1/PD–L1 treatment, with an aim to provide a new strategy for clinically efficient and convenient screening of colorectal cancer patient who would benefit from immunotherapy and therapeutic evaluation of immunotherapy.