Dong Chengyuan, Lin Ziyou, Hu Yunzhao, Lu Qun
Shanghai TCM-Integrated Hospital, Shanghai university of TCM, Shanghai, China.
Tongji University School of Medicine, Shanghai, China.
J Cancer. 2025 Jan 1;16(3):982-995. doi: 10.7150/jca.104762. eCollection 2025.
Killer Cell Lectin Like Receptor D1 (KLRD1) plays a crucial role in antitumor immunity. However, its expression patterns across various cancers, its relationship with patient prognosis, and its potential as an immunotherapy target remain inadequately understood. We analyzed KLRD1 expression across various cancer types using multi-omics data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases, correlating it with patient prognosis. Single-cell RNA sequencing data were employed to further explore KLRD1 expression in natural killer (NK) cells and exhausted CD8+ T cells (CD8Tex). Functional enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) identified the biological processes and pathways associated with KLRD1. Immune infiltration analysis, conducted via CIBERSORT, assessed the relationship between KLRD1 expression and immune cell infiltration within the tumor microenvironment. Furthermore, the Tracking Tumor Immunophenotype (TIP) meta-server and Easier tool were employed to assess the role of KLRD1 in the cancer immunity cycle and to predict immunotherapy responses. Drug sensitivity was predicted using tools like CellMiner and the Genomics of Drug Sensitivity in Cancer (GDSC) database to explore the link between KLRD1 expression and responsiveness to various anticancer drugs. KLRD1 exhibits significant differential expression and strong prognostic value across cancers, particularly as an independent prognostic factor in head and neck squamous cell carcinoma (HNSC). Single-cell analysis revealed high expression of KLRD1 in NK and CD8Tex cells, indicating its critical role in antitumor immune responses. Functional enrichment analyses showed that KLRD1 is involved in several immune-related signaling pathways, including NK cell-mediated cytotoxicity and T cell receptor pathways. Immune infiltration analysis further confirmed a positive correlation between KLRD1 expression and the infiltration of various immune cells. Moreover, higher KLRD1 expression in HNSC is associated with enhanced immune pathway activity, increased sensitivity to cell division inhibitors, and the identification of arachidonyltrifluoromethane as a potential compound to counteract its oncogenic effects. In HNSC, KLRD1 is a key prognostic marker and potential target for personalized immunotherapy.
杀伤细胞凝集素样受体D1（KLRD1）在抗肿瘤免疫中起着至关重要的作用。然而，其在各种癌症中的表达模式、与患者预后的关系以及作为免疫治疗靶点的潜力仍未得到充分了解。我们使用来自癌症基因组图谱（TCGA）、基因型-组织表达（GTEx）和基因表达综合数据库（GEO）的多组学数据，分析了KLRD1在各种癌症类型中的表达，并将其与患者预后相关联。利用单细胞RNA测序数据进一步探索KLRD1在自然杀伤（NK）细胞和耗竭性CD8 + T细胞（CD8Tex）中的表达。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）进行功能富集分析，确定与KLRD1相关的生物学过程和途径。通过CIBERSORT进行免疫浸润分析，评估KLRD1表达与肿瘤微环境中免疫细胞浸润之间的关系。此外，利用肿瘤免疫表型追踪（TIP）元服务器和Easier工具评估KLRD1在癌症免疫循环中的作用，并预测免疫治疗反应。使用CellMiner和癌症药物敏感性基因组学（GDSC）数据库等工具预测药物敏感性，以探索KLRD1表达与对各种抗癌药物反应性之间的联系。KLRD1在各种癌症中表现出显著的差异表达和强大的预后价值，特别是在头颈部鳞状细胞癌（HNSC）中作为独立的预后因素。单细胞分析显示KLRD1在NK细胞和CD8Tex细胞中高表达，表明其在抗肿瘤免疫反应中的关键作用。功能富集分析表明，KLRD1参与了多个免疫相关信号通路，包括NK细胞介导的细胞毒性和T细胞受体通路。免疫浸润分析进一步证实了KLRD1表达与各种免疫细胞浸润之间的正相关。此外，HNSC中较高的KLRD1表达与免疫途径活性增强、对细胞分裂抑制剂的敏感性增加以及将花生四烯酰三氟甲烷鉴定为抵消其致癌作用的潜在化合物有关。在HNSC中，KLRD1是关键的预后标志物和个性化免疫治疗的潜在靶点。
