PDF(Pubmed)
Abstract：
UNASSIGNED: The combination of agonistic antibodies with immune checkpoint inhibitors presents a promising avenue for cancer immunotherapy. Our objective is to explore the co-expression of 4-1BB, ICOS, CD28, with PD-1 on CD8+ T cells in the peripheral blood and tumor tissue of cervical cancer(CC) patients, with a specific focus on the association between the co-expression levels of 4-1BB with PD-1 and clinical features, prognosis as well as immunotherapy response. The goal is to offer valuable insights into cervical cancer immunotherapy.
UNASSIGNED: In this study, 50 treatment-naive patients diagnosed with CC were enrolled. Flow cytometry was used to detect PD-1/4-1BB, PD-1/ICOS and PD-1/CD28 co-expression on CD8+ T cells. Subsequent analysis aimed to investigate the differential co-expression between peripheral blood and cancer tissue, and also the correlation between co-expression and clinical features in these patients. Gene Expression Omnibus (GEO) datasets, The Cancer Genome Atlas (TCGA) cohort, The IMvigor210 cohort, The BMS038cohort and Immunophenoscores were utilized to investigate the correlation between PD-1/4-1BB and the immune microenvironment, prognosis, immunotherapy, and drug sensitivity in cervical cancer.
UNASSIGNED: The co-expression levels of PD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 on CD8+ tumor-infiltrating lymphocytes (TILs) were significantly higher in cervical cancer patients compared to those in peripheral blood. Clinical feature analysis reveals that on CD8+ TILs, the co-expression of PD-1/4-1BB is more closely correlated with clinical characteristics compared to PD-1/ICOS, PD-1/CD28, PD-1, and 4-1BB. Pseudo-time analysis and cell communication profiling reveal close associations between the subgroups harboring 4-1BB and PD-1. The prognosis, tumor mutation burden, immune landscape, and immunotherapy response exhibit statistically significant variations between the high and low co-expression groups of PD-1/4-1BB. The high co-expression group of PD-1/4-1BB is more likely to benefit from immunotherapy.
UNASSIGNED: PD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 exhibit elevated co-expression on CD8+TILs of cervical cancer, while demonstrating lower expression in circulating T cells. The co-expression patterns of PD-1/4-1BB significantly contributed to the prediction of immune cell infiltration characteristics, prognosis, and tailored immunotherapy tactics. PD-1/4-1BB exhibits potential as a target for combination immunotherapy in cervical cancer.
UNASSIGNED: In this study, 50 treatment-naive patients diagnosed with CC were enrolled. Flow cytometry was used to detect PD-1/4-1BB, PD-1/ICOS and PD-1/CD28 co-expression on CD8+ T cells. Subsequent analysis aimed to investigate the differential co-expression between peripheral blood and cancer tissue, and also the correlation between co-expression and clinical features in these patients. Gene Expression Omnibus (GEO) datasets, The Cancer Genome Atlas (TCGA) cohort, The IMvigor210 cohort, The BMS038cohort and Immunophenoscores were utilized to investigate the correlation between PD-1/4-1BB and the immune microenvironment, prognosis, immunotherapy, and drug sensitivity in cervical cancer.
UNASSIGNED: The co-expression levels of PD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 on CD8+ tumor-infiltrating lymphocytes (TILs) were significantly higher in cervical cancer patients compared to those in peripheral blood. Clinical feature analysis reveals that on CD8+ TILs, the co-expression of PD-1/4-1BB is more closely correlated with clinical characteristics compared to PD-1/ICOS, PD-1/CD28, PD-1, and 4-1BB. Pseudo-time analysis and cell communication profiling reveal close associations between the subgroups harboring 4-1BB and PD-1. The prognosis, tumor mutation burden, immune landscape, and immunotherapy response exhibit statistically significant variations between the high and low co-expression groups of PD-1/4-1BB. The high co-expression group of PD-1/4-1BB is more likely to benefit from immunotherapy.
UNASSIGNED: PD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 exhibit elevated co-expression on CD8+TILs of cervical cancer, while demonstrating lower expression in circulating T cells. The co-expression patterns of PD-1/4-1BB significantly contributed to the prediction of immune cell infiltration characteristics, prognosis, and tailored immunotherapy tactics. PD-1/4-1BB exhibits potential as a target for combination immunotherapy in cervical cancer.
摘要：
■激动性抗体与免疫检查点抑制剂的组合为癌症免疫治疗提供了有希望的途径。我们的目标是探索4-1BB的共表达，ICOS,CD28、PD-1对宫颈癌(CC)患者外周血和肿瘤组织中CD8+T细胞,特别关注4-1BB与PD-1的共表达水平与临床特征之间的关联，预后以及免疫治疗反应。我们的目标是为宫颈癌免疫治疗提供有价值的见解。
■在这项研究中，纳入50名诊断为CC的未接受治疗的患者。流式细胞仪检测PD-1/4-1BB,PD-1/ICOS和PD-1/CD28在CD8+T细胞上共表达。随后的分析旨在研究外周血和癌组织之间的差异共表达。以及这些患者的共表达与临床特征之间的相关性。基因表达综合(GEO)数据集，癌症基因组图谱（TCGA）队列，IMVESPOW210队列，BMS038队列和免疫表型用于研究PD-1/4-1BB和免疫微环境之间的相关性。预后,免疫疗法，宫颈癌的药物敏感性。
■PD-1/4-1BB的共表达水平，PD-1/ICOS,与外周血相比，宫颈癌患者的CD8+肿瘤浸润淋巴细胞（TIL）上的PD-1/CD28明显更高。临床特征分析显示，在CD8+TIL上，与PD-1/ICOS相比，PD-1/4-1BB的共表达与临床特征更密切相关，PD-1/CD28、PD-1和4-1BB。伪时间分析和细胞通讯分析揭示了携带4-1BB和PD-1的亚组之间的紧密关联。预后，肿瘤突变负荷，免疫景观，和免疫疗法反应在PD-1/4-1BB的高和低共表达组之间表现出统计学上的显着差异。PD-1/4-1BB的高共表达组更有可能受益于免疫治疗。
■PD-1/4-1BB,PD-1/ICOS,和PD-1/CD28在宫颈癌的CD8+TIL上表现出升高的共表达，在循环T细胞中表达较低。PD-1/4-1BB的共表达模式显著有助于预测免疫细胞浸润特征，预后,和量身定制的免疫疗法策略。PD-1/4-1BB显示出作为宫颈癌联合免疫疗法靶标的潜力。
■在这项研究中，纳入50名诊断为CC的未接受治疗的患者。流式细胞仪检测PD-1/4-1BB,PD-1/ICOS和PD-1/CD28在CD8+T细胞上共表达。随后的分析旨在研究外周血和癌组织之间的差异共表达。以及这些患者的共表达与临床特征之间的相关性。基因表达综合(GEO)数据集，癌症基因组图谱（TCGA）队列，IMVESPOW210队列，BMS038队列和免疫表型用于研究PD-1/4-1BB和免疫微环境之间的相关性。预后,免疫疗法，宫颈癌的药物敏感性。
■PD-1/4-1BB的共表达水平，PD-1/ICOS,与外周血相比，宫颈癌患者的CD8+肿瘤浸润淋巴细胞（TIL）上的PD-1/CD28明显更高。临床特征分析显示，在CD8+TIL上，与PD-1/ICOS相比，PD-1/4-1BB的共表达与临床特征更密切相关，PD-1/CD28、PD-1和4-1BB。伪时间分析和细胞通讯分析揭示了携带4-1BB和PD-1的亚组之间的紧密关联。预后，肿瘤突变负荷，免疫景观，和免疫疗法反应在PD-1/4-1BB的高和低共表达组之间表现出统计学上的显着差异。PD-1/4-1BB的高共表达组更有可能受益于免疫治疗。
■PD-1/4-1BB,PD-1/ICOS,和PD-1/CD28在宫颈癌的CD8+TIL上表现出升高的共表达，在循环T细胞中表达较低。PD-1/4-1BB的共表达模式显著有助于预测免疫细胞浸润特征，预后,和量身定制的免疫疗法策略。PD-1/4-1BB显示出作为宫颈癌联合免疫疗法靶标的潜力。
