Proteomics in PD1-LAG3 biology

T-cell lines with constitutively active PD-1, LAG-3 pathways or their combination were generated to drive distinct types of T-cell dysfunctionality. Global changes were cross-evaluated among T-cell lines and with the multiomic data from human cancers. Regulated genetic, metabolic and proteomic programmes of strong dysfunctionality in T cells and human cancers were identified at multiple levels.构建了携带组成型激活的程序性死亡受体1（PD-1）、淋巴细胞活化基因3（LAG-3）信号通路或二者联合激活的T细胞系，以诱导不同类型的T细胞功能失调。研究对各T细胞系的全局分子变化进行了跨组交叉评估，并将其与人类癌症的多组学（multiomic）数据开展联合比对分析。本研究从多个层面鉴定出了与T细胞及人类癌症中重度功能失调相关的受调控遗传、代谢及蛋白质组学调控程序。