一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Characterization of TCF-1 and its relationship between CD8+ TIL densities and immune checkpoints and their joint influences on prognoses of lung adenocarcinoma patients.
Characterization of TCF-1 and its relationship between CD8+ TIL densities and immune checkpoints and their joint influences on prognoses of lung adenocarcinoma patients.
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TCF-1 在 LUAD 患者中具有相对较高的阳性表达和特殊的临床病理特征。TCF-1+ TIL 与 CD8 密度、TIM-3 表达、LAG-3 表达和 PD-1 表达相关,并与 LUAD 患者较好的预后相关。TCF-1 与 CD8 密度或 PD-1 表达的联合进一步将患者分层为具有不同预后的不同组别。
T细胞因子-1(TCF-1)+干细胞样TIL(肿瘤浸润淋巴细胞)(干细胞样TILs)是肿瘤微环境中重要的记忆细胞。然而,它们与肺腺癌(LUADs)的临床病理特征、CD8+ TIL密度、免疫检查点抑制剂(ICs)及预后价值的关系尚不清楚。在本研究中,我们旨在表征TCF-1+ TILs及其在手术切除LUADs患者中的预后意义。
采用免疫组织化学方法检测切除的LUAD中TILs的TCF-1、CD8及ICs(包括PD-1、LAG-3和TIM-3)的表达。分析TCF-1表达与患者预后临床病理特征之间的关联。
TCF-1阳性表达与晚期病理分期、肿瘤分级、CD8+ TILs密度、TIM-3表达、LAG-3表达和PD-1表达显著相关。TCF-1阳性与更好的无复发生存期(RFS)和总生存期(OS)显著相关。亚组分析显示,TCF-1+/CD8+组具有最佳的RFS和OS,而TCF-1-/CD8-组具有最差的RFS和OS。同样,TCF-1+PD-1-患者的预后最佳,TCF-1-PD-1+患者的预后最差。
T cell factor-1 (TCF-1) + stem-like tumor-infiltrating lymphocytes (stem-like TILs) are important memory cells in the tumor microenvironment. However, their relationship with clinicopathological features, CD8+ TIL densities, immune checkpoint inhibitors (ICs), and prognostic values remain unknown for lung adenocarcinomas (LUADs). In this study, we aimed to characterize TCF-1+ TILs and their prognostic significance in patients with surgically resected LUADs.
Expression of TCF-1, CD8, and ICs including programmed death-1 (PD-1), lymphocyte activating-3 (LAG-3), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3) in TILs were estimated using immunohistochemistry of resected LUADs. The association between TCF-1 expressions and clinicopathological characteristics of patient prognoses were analyzed.
Positive TCF-1 expression significantly correlated with advanced pathological stage, tumor grade, CD8+ TILs density, TIM-3 expression, LAG-3 expression, and PD-1 expression. TCF-1 positivity was significantly associated with a better recurrence-free survival (RFS), and overall survival (OS). Subgroup analysis revealed that the TCF-1+/CD8+ group had the best RFS and OS, while the TCF-1-/CD8- group had the worst RFS and OS. Similarly, patients with TCF-1 + PD-1- had the best prognoses and patients with TCF-1-PD-1+ had the worst prognoses.
TCF-1 had relatively high positive expression and special clinicopathological features in patients with LUAD. TCF-1+ TILs were related to CD8 density, TIM-3 expression, LAG-3 expression, and PD-1 expression, and were associated with better prognoses in LUAD patients. A combination of TCF-1 and CD8 densities or PD-1 expression further stratified patients into different groups with distinct prognoses.
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