Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predic...Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8^(+)T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS 2,and TNFRSF1B was constructed.The risk score model was well validated through an independent external validation cohort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8^(+)T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity analysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene model was verified by immunohistochemistry.In summary,the establishment and validation of a CD8^(+)T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.展开更多
为探讨人参总皂甙(totalsaponins of panaxginseng,TSPG)协同造血生长因子体外诱导CD34+造血干/祖细胞(HSC/HPC)扩增与分化的作用,收集人脐血、骨髓细胞并采用StemsepTM干细胞分选系统分离纯化CD34+HSC/HPC,用不同剂量TSPG加入不同组合...为探讨人参总皂甙(totalsaponins of panaxginseng,TSPG)协同造血生长因子体外诱导CD34+造血干/祖细胞(HSC/HPC)扩增与分化的作用,收集人脐血、骨髓细胞并采用StemsepTM干细胞分选系统分离纯化CD34+HSC/HPC,用不同剂量TSPG加入不同组合的造血生长因子进行培养,检测细胞总数、CD34+细胞和CD33+细胞比例及集落形成细胞总数(CFC)、粒系祖细胞(CFU-GM)数量变化。结果显示:10-70μg/mlTSPG均可不同程度地提高脐血细胞总数、CFC数和CD34+细胞数,50μg/ml是最佳刺激浓度,可使细胞总数、CFC数和CD34+细胞数分别增至(2470.5±79.96)×103、(53.96±4.29)×100%和(21.86±3.09)×100%;20μg/ml是液体培养诱导骨髓CD34+细胞向粒系分化的最佳浓度,可使细胞总数、CFU-GM和CD33+细胞分别增至(133.2±9.03)×103、(26.78±1.91)×100%和(16.98±1.73)×100%;甲基纤维素半固体培养检测显示,TSPG(10-50μg/ml)均能提高CD34+细胞形成CFU-GM的集落产率,以TSPG20μg/ml效果最为明显。结论:合适剂量的TSPG能够促进CD34+造血干/祖细胞体外扩增与定向诱导分化。展开更多
基金国家自然科学基金项目(No.81902513)山西省应用基础研究计划项目(No.202303021211114 and 202103021224228)山西省高等教育百亿工程“科技引导”专项(No.BYJL047)资助。
文摘Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8^(+)T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS 2,and TNFRSF1B was constructed.The risk score model was well validated through an independent external validation cohort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8^(+)T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity analysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene model was verified by immunohistochemistry.In summary,the establishment and validation of a CD8^(+)T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.
文摘为探讨人参总皂甙(totalsaponins of panaxginseng,TSPG)协同造血生长因子体外诱导CD34+造血干/祖细胞(HSC/HPC)扩增与分化的作用,收集人脐血、骨髓细胞并采用StemsepTM干细胞分选系统分离纯化CD34+HSC/HPC,用不同剂量TSPG加入不同组合的造血生长因子进行培养,检测细胞总数、CD34+细胞和CD33+细胞比例及集落形成细胞总数(CFC)、粒系祖细胞(CFU-GM)数量变化。结果显示:10-70μg/mlTSPG均可不同程度地提高脐血细胞总数、CFC数和CD34+细胞数,50μg/ml是最佳刺激浓度,可使细胞总数、CFC数和CD34+细胞数分别增至(2470.5±79.96)×103、(53.96±4.29)×100%和(21.86±3.09)×100%;20μg/ml是液体培养诱导骨髓CD34+细胞向粒系分化的最佳浓度,可使细胞总数、CFU-GM和CD33+细胞分别增至(133.2±9.03)×103、(26.78±1.91)×100%和(16.98±1.73)×100%;甲基纤维素半固体培养检测显示,TSPG(10-50μg/ml)均能提高CD34+细胞形成CFU-GM的集落产率,以TSPG20μg/ml效果最为明显。结论:合适剂量的TSPG能够促进CD34+造血干/祖细胞体外扩增与定向诱导分化。
