PDF(Pubmed)
Abstract：
T cells are essential tumor suppressors in cancer immunology, but their dysfunction induced by cancer cells can result in T cell exhaustion. Exhausted T cells (Tex) significantly influence the tumor immune environment, and thus, there is a need for their thorough investigation across different types of cancer. Here, we address the role of Tex cells in pan-cancer, focusing on the expression, mutations, methylation, immune infiltration, and drug sensitivity of a molecular signature comprising of the genes HAVCR2, CXCL13, LAG3, LAYN, TIGIT, and PDCD1across multiple cancer types, using bioinformatics analysis of TCGA data. Our analysis revealed that the Tex signature genes are differentially expressed across 14 cancer types, being correlated with patient survival outcomes, with distinct survival trends. Pathway analysis indicated that the Tex genes influence key cancer-related pathways, such as apoptosis, EMT, and DNA damage pathways. Immune infiltration analysis highlighted a positive correlation between Tex gene expression and immune cell infiltration in bladder cancer, while mutations in these genes were associated with specific immune cell enrichments in UCEC and SKCM. CNVs in Tex genes were widespread across cancers. We also highlight high LAYN methylation in most tumors and a negative correlation between methylation levels and immune cell infiltration in various cancers. Drug sensitivity analysis identified numerous correlations, with CXCL13 and HAVCR2 expressions influencing sensitivity to several drugs, including Apitolisib, Belinostat, and Docetaxel. Overall, these findings highlight the importance of reviving exhausted T cells to enhance the treatment efficacy to significantly boost anti-tumor immunity and achieve better clinical outcomes.
摘要：
T细胞是癌症免疫学中必不可少的肿瘤抑制因子，但是它们由癌细胞诱导的功能障碍会导致T细胞耗尽。耗竭T细胞(Tex)显著影响肿瘤免疫环境,因此，有必要对不同类型的癌症进行彻底调查。这里,我们讨论了Tex细胞在泛癌症中的作用，专注于表达，突变,甲基化,免疫浸润，和包含基因HAVCR2，CXCL13，LAG3，LAYN，TIGIT,和PDCD1跨越多种癌症类型，利用生物信息学分析TCGA数据。我们的分析显示，Tex标记基因在14种癌症类型中差异表达，与患者生存结果相关，有明显的生存趋势。通路分析表明，Tex基因影响关键的癌症相关通路，如细胞凋亡，EMT,和DNA损伤途径。免疫浸润分析强调了膀胱癌中Tex基因表达与免疫细胞浸润之间的正相关，而这些基因的突变与UCEC和SKCM中的特异性免疫细胞富集有关。Tex基因中的CNV在癌症中普遍存在。我们还强调了大多数肿瘤中的高LAYN甲基化以及各种癌症中甲基化水平与免疫细胞浸润之间的负相关。药物敏感性分析确定了许多相关性，CXCL13和HAVCR2表达影响对几种药物的敏感性，包括Apitolisib,Belinostat,和多西他赛。总的来说,这些研究结果强调了恢复耗尽的T细胞对于增强治疗效果以显着增强抗肿瘤免疫力并获得更好临床结局的重要性.
