CD30信号抑制肠道肿瘤免疫微环境CD8+T细胞TIGIT及LAG-3表达促进CTL介导抗肿瘤免疫应答机制研究

我国结直肠癌发病率和死亡率逐年上升，2020年中国新发结直肠癌占中国新确诊癌症总数的12.2%，因此探索结直肠癌生物标志物及可能发病机制至关重要。前期研究基础明确CD30信号缺失肠道肿瘤负荷加重，NF-κB通路活化程度增高，IRF4表达上调，CD8+T细胞表达TIGIT、LAG-3增多。此外，生信预测IRF4可识别TIGIT和LAG-3同一启动子识别位点调控其转录。综上，申请人提出科学假说，CD30信号通过抑制NF-κB通路抑制转录因子IRF4转录调控TIGIT、LAG-3，促进肿瘤免疫微环境CD8+T细胞杀伤功能，在结直肠癌形成中发挥抗肿瘤免疫应答调控作用。本研究的开展将对以CD30信号为靶向的肠道肿瘤的免疫生物学治疗方法开发与利用提供新的理论依据和研究思路。

The incidence and mortality of colorectal cancer in China are increasing year by year. In 2020, the incidence rate of new colorectal cancer in China accounted for 12.2% of the total number of newly diagnosed cancers in China. Therefore, it is very important to explore the biomarkers and possible pathogenesis of colorectal cancer. Previous studies showed that the lack of CD30 signal aggravated the burden of intestinal tumor, increased the activation of NF-κB pathway, up-regulated the expression of IRF4, and increased the expression of TIGIT and LAG-3 on CD8+ T cells. In addition, Bioinformatics analysis predicted that IRF4 could recognize the same promoter recognition site of TIGIT and LAG-3 and regulate its transcription. In conclusion, the applicant put forward a scientific hypothesis that CD30 signal inhibit the transcription of transcription factor IRF4 by inhibiting NF-κB pathway, regulate TIGIT and LAG-3, promote the killing function of CD8+ T cells in tumor immune microenvironment, and play a regulatory role in anti-tumor immune response in the formation of colorectal cancer. The development of this study will provide a new theoretical basis and research ideas for the development and utilization of immunobiological therapy for intestinal tumors targeting CD30 signal.