为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prognostic significance of programmed cell death-ligand 1 expression on immune cells and epithelial-mesenchymal transition expression in patients with hepatocellular carcinoma.
Prognostic significance of programmed cell death-ligand 1 expression on immune cells and epithelial-mesenchymal transition expression in patients with hepatocellular carcinoma.
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本研究表明,肝细胞癌中 TILs 的 PD-L1 表达与上皮-间质转化标志物的表达密切相关。
免疫检查点抑制剂(ICI)已显著改善多种癌症的肿瘤学结局,但其在肝细胞癌(HCC)中的应用仍处于早期。程序性死亡配体1(PD-L1)、TIL(肿瘤浸润淋巴细胞)和上皮-间质转化(EMT)标志物均被认为是HCC预后因素。因此,本研究重点分析这些指标间的分子机制,以评估其预测作用。
收集166名接受手术的HCC患者福尔马林固定石蜡包埋组织,通过免疫组化评估PD-L1、TIL及EMT标志物表达。
多变量分析显示,TIL表达是总生存期的独立预后因素(风险比[HR]0.483;95%置信区间[CI]0.269–0.866;P=0.015),EMT标志物表达是无病生存期的预后因素(HR 1.565;95% CI 1.019–2.403;P=0.005)。与TIL低表达患者相比,TIL高表达患者生存显著更好(P=0.023)。TIL阳性/EMT阴性患者的预后显著优于TIL阴性/EMT阳性患者(P=0.049)。
本研究显示,HCC患者TIL中的PD-L1表达与EMT标志物表达密切相关。值得在EMT相关PD-L1上调患者中开展抗PD-1/PD-L1抑制剂临床研究。
Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers. However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role.
Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis.
The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269-0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019-2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT- showed a significantly better prognosis than those who were TIL-/EMT+ (P = 0.049).
This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti-PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.
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