目的探究CD161(killer cell lectin like receptor B1,KLRB1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及与预后、免疫浸润的相关性。方法通过The Cancer Genome Atlas(TCGA),TIMER数据库进行回顾性RNA-seq数据分析CD161在HCC...目的探究CD161(killer cell lectin like receptor B1,KLRB1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及与预后、免疫浸润的相关性。方法通过The Cancer Genome Atlas(TCGA),TIMER数据库进行回顾性RNA-seq数据分析CD161在HCC组织中的表达及其与临床病理特征的相关性,RT-qPCR进一步验证CD161表达;HPA和GeneCards分析CD161蛋白表达水平与亚细胞定位;TCGA与KM Plotter用来评估HCC中CD161表达与预后的关系;利用Single Cell Expression Atlas(SCEA)数据库测序分析CD161在组织细胞中的富集水平;应用DAVID 6.8软件对CD161及关联基因进行GO和KEGG富集分析,GSEA(Gene-Set Enrichment Analysis)软件预测CD161参与的信号通路;GSCA(Gene Set Cancer Analysis)分析CD161与肿瘤微环境中细胞免疫浸润的关系。结果与正常肝组织相比,CD161在HCC中显著低表达(主要定位于细胞膜),且与患者良好预后正相关。GO与KEGG富集分析显示CD161主要参与免疫反应,且在脂肪酸生物合成、NF-κB信号传导途径、造血干细胞和线型特异性标志物及先天性淋巴细胞的分化中发挥关键作用。单细胞测序结果显示CD161主要富集于T细胞中,且与HCC肿瘤微环境中多个免疫细胞浸润显著相关,其中包括Tfh细胞(r=0.90,FDR=5.41×10^(-146))、中性粒细胞(r=-0.74,FDR=5.10×10^(-71))、NK细胞(r=0.63,FDR=6.99×10^(-46))、Th1细胞(r=0.53,FDR=2.91×10^(-30))等。结论CD161在HCC中表达下调,且与患者良好预后及免疫浸润显著相关。因此,CD161可作为判断预后的潜在标志物,是未来HCC临床免疫治疗中有意义的新靶点。展开更多
Breast and prostate cancer are the leading causes of death in females and males, respectively. Triple negative breast cancer (TNBC) does not express the estrogen receptor, progesterone receptor, or human epidermal gro...Breast and prostate cancer are the leading causes of death in females and males, respectively. Triple negative breast cancer (TNBC) does not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2, resulting in limited treatment options. Androgen deprivation therapy is the standard care for prostate cancer patients;however, metastasis and recurrence are seen in androgen-independent prostate cancer. Both prostate and breast cancer show higher resistance after recurrence and metastasis, which increases the difficulty of treatment. Natural killer (NK) cells play a critical role during innate immunity and tumor recognition and elimination. NK cell function is determined by a delicate balance of inhibitory signals and activation signals received through cell surface receptors. Lectin-like transcript 1 (LLT1, CLEC2D, OCIL) is a ligand of NK cell inhibitory receptor NKRP1A (CD161). Several studies have that reported higher expression of LLT1 is associated with the development of various tumors. Our studies revealed that TNBC and prostate cancer cells express higher levels of LLT1. In the presence of a monoclonal antibody against LLT1, NK cell-mediated killing of TNBC and prostate cancer cells were greatly enhanced. This review highlights the potential that using monoclonal antibodies to block LLT1 - NKRP1A interactions could be an effective immunotherapeutic approach to treat triple negative breast cancer and prostate cancer.展开更多
文摘目的探究CD161(killer cell lectin like receptor B1,KLRB1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及与预后、免疫浸润的相关性。方法通过The Cancer Genome Atlas(TCGA),TIMER数据库进行回顾性RNA-seq数据分析CD161在HCC组织中的表达及其与临床病理特征的相关性,RT-qPCR进一步验证CD161表达;HPA和GeneCards分析CD161蛋白表达水平与亚细胞定位;TCGA与KM Plotter用来评估HCC中CD161表达与预后的关系;利用Single Cell Expression Atlas(SCEA)数据库测序分析CD161在组织细胞中的富集水平;应用DAVID 6.8软件对CD161及关联基因进行GO和KEGG富集分析,GSEA(Gene-Set Enrichment Analysis)软件预测CD161参与的信号通路;GSCA(Gene Set Cancer Analysis)分析CD161与肿瘤微环境中细胞免疫浸润的关系。结果与正常肝组织相比,CD161在HCC中显著低表达(主要定位于细胞膜),且与患者良好预后正相关。GO与KEGG富集分析显示CD161主要参与免疫反应,且在脂肪酸生物合成、NF-κB信号传导途径、造血干细胞和线型特异性标志物及先天性淋巴细胞的分化中发挥关键作用。单细胞测序结果显示CD161主要富集于T细胞中,且与HCC肿瘤微环境中多个免疫细胞浸润显著相关,其中包括Tfh细胞(r=0.90,FDR=5.41×10^(-146))、中性粒细胞(r=-0.74,FDR=5.10×10^(-71))、NK细胞(r=0.63,FDR=6.99×10^(-46))、Th1细胞(r=0.53,FDR=2.91×10^(-30))等。结论CD161在HCC中表达下调,且与患者良好预后及免疫浸润显著相关。因此,CD161可作为判断预后的潜在标志物,是未来HCC临床免疫治疗中有意义的新靶点。
文摘Breast and prostate cancer are the leading causes of death in females and males, respectively. Triple negative breast cancer (TNBC) does not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2, resulting in limited treatment options. Androgen deprivation therapy is the standard care for prostate cancer patients;however, metastasis and recurrence are seen in androgen-independent prostate cancer. Both prostate and breast cancer show higher resistance after recurrence and metastasis, which increases the difficulty of treatment. Natural killer (NK) cells play a critical role during innate immunity and tumor recognition and elimination. NK cell function is determined by a delicate balance of inhibitory signals and activation signals received through cell surface receptors. Lectin-like transcript 1 (LLT1, CLEC2D, OCIL) is a ligand of NK cell inhibitory receptor NKRP1A (CD161). Several studies have that reported higher expression of LLT1 is associated with the development of various tumors. Our studies revealed that TNBC and prostate cancer cells express higher levels of LLT1. In the presence of a monoclonal antibody against LLT1, NK cell-mediated killing of TNBC and prostate cancer cells were greatly enhanced. This review highlights the potential that using monoclonal antibodies to block LLT1 - NKRP1A interactions could be an effective immunotherapeutic approach to treat triple negative breast cancer and prostate cancer.
