肿瘤免疫治疗作为一种有效的治疗模式是目前肿瘤领域的研究热点。重要的免疫检查点蛋白PD-L1参与肿瘤免疫调控，在肺癌等多种肿瘤表达异常增高。临床试验结果表明，抗PD-1/PD-L1抗体在肺癌治疗中呈现良好治疗效果。因此，阐明PD-L1蛋白调节机制对进一步深入研究具有关键意义。经典促炎因子MIF被认为是连接慢性炎症与肿瘤的关键的蛋白。我们前期研究发现，MIF高表达与肺癌的不良预后正相关，过表达MIF显著增加肺癌细胞PD-L1蛋白表达量。然而，MIF调节PD-L1确切的分子机制尚不明确。因此，我们拟采用体内和体外模型，从分子-细胞-动物三个层次明确MIF是否通过PD-L1调控肿瘤免疫，并阐明MIF上调PD-L1的分子机制。在此基础上，我们还将评价靶向MIF的先导多肽Pep2-MIFA对肿瘤免疫逃逸的影响及其抗肿瘤活性。本研究不但有助揭示PD-L1的免疫调节机制，同时也为抗肿瘤药物研发提供新思路。

Tumor immunotherapy as an effective cancer treatment model is extensively investigated. Immune checkpoint protein PD-L1 is involved in tumor immune regulation. High-level expression of PD-L1 associates with lung cancer and many other cancers. In recent clinical trials, anti-PD-1 or anti-PD-L1 antibodies provide promising therapeutic efficiency for lung cancer. Therefore, understanding the regulatory mechanism of PD-L1 may clarify mechanisms of immune escape and/or develop novel strategies for lung cancer. It is recently found that MIF, a classic proinflammatory cytokine, links chronic inflammation with cancer development. Our pilot results showed that high-level of the expression of MIF positively associates with poor prognosis of lung cancer. Moreover, overexpression of MIF significantly increased the expression of PD-L1 in lung cancer cells. However, the molecular mechanisms of MIF-regulated PD-L1 are still unclear. Here, we propose to use the in vivo and in vitro models to investigate the potential roles and molecular mechanisms of MIF in the regulation of tumor escape through upregulation of PD-L1. We will also evaluate the effect of peptide Pep2-MIFA on tumor immune escape and its anti-tumor effect. Our proposed studies may not only provide deep insights in the mechanisms of PD-L1 regulation, but may also provide opportunities for the development of anti-cancer drugs.