研究参与免疫逃逸的重要基因并阐明其分子机制，对食管鳞癌的诊治具有重要意义。本项目前期发现MAGE-C3在食管鳞癌基因组中具有显著扩增并在食管鳞癌组织中高表达。功能实验发现MAGE-C3不仅促进肿瘤转移还能抵抗免疫细胞对肿瘤的杀伤作用。初步研究提示MAGE-C3的功能与IFN-γ响应有关，同时还验证了MAGE-C3能对PD-L1的表达进行调控，但具体机制尚不明确。综上，本项目提出假说：MAGE-C3在食管鳞癌中激活IFN-γ通路上调PD-L1，从而导致肿瘤免疫抑制。本项目拟从分子及细胞水平阐明MAGE-C3对IFN-γ通路的调控机制以及MAGE-C3是否通过PD-L1调控肿瘤免疫，然后从动物水平明确MAGE-C3对肿瘤免疫逃逸的作用，最后结合食管鳞癌标本探讨MAGE-C3的临床意义。本研究将揭示MAGE-C3参与调控食管鳞癌免疫逃逸的分子机制，为食管鳞癌新型免疫疗法的开发提供新思路。

Given the advanced immunotherapy is still lacking in esophageal squamous cell carcinoma (ESCC), there is a need to identify the molecular mechanism of high-risk genes involved in tumor immune evasion, which is critical for diagnosis and treatment in ESCC. In previous work, we figured out that melanoma-associated antigen C3 (MAGE-C3) presented highlighted genomic amplification, and we also confirmed that MAGE-C3 was overexpressed in ESCC tissue compared with adjacent tissue. Additionally, MAGE-C3 promoted tumor metastasis and inhibited the anti-tumor function of immune cells. In preliminary study, it was revealed that MAGE-C3 functioned in IFN-γ response and MAGE-C3 could regulate PD-L1 expression. Collectively, we hypothesized that MAGE-C3 might activate IFN-γ pathway and then upregulate downstream PD-L1 in ESCC, resulting in tumor immunosuppression. Therefore, our project proposes to use molecular-to-cell models to investigate the potential mechanisms of MAGE-C3 in the regulation of IFN-γ pathway and determine whether the tumor immune regulation of MAGE-C3 may be mediated by PD-L1. We will also elucidate the effect of MAGE-C3 on tumor immune escape in vitro and explore its clinical significance in ESCC tissues. Our study would reveal the immune evasion mechanism of MAGE-C3 and provide a new approach for the treatment of ESCC.