更正:B7-H3 CAR-T 细胞清除肝内胆管癌并诱导持久应答
Correction: B7-H3 CAR T cells eradicate intrahepatic cholangiocarcinoma and induce durable response.
英文原题:Immune and Histopathological Biomarkers for Prognosis and Neoadjuvant Immunotherapy Response in Intrahepatic Cholangiocarcinoma.
Immune and Histopathological Biomarkers for Prognosis and Neoadjuvant Immunotherapy Response in Intrahepatic Cholangiocarcinoma.
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这些发现为患者分层提供了关键见解,并凸显了优化 iCCA 患者免疫靶向治疗的潜力。
对34例接受切除的iCCA病例进行免疫荧光分析,评估CD8+ T细胞和Treg密度,并分析其与生存、免疫及组织病理特征的统计学相关性。另在独立队列的95份新辅助治疗(NAT)前iCCA活检样本中验证,以评估免疫和组织病理特征对生存及NAT应答的预测价值。
切除病例队列的免疫荧光分析显示,CD8+ T细胞浸润增加与生存改善相关(P=.018),支持其抗肿瘤免疫作用。相反,Treg密度较高与生存较差相关(P=.038),提示其可能促进肿瘤并发挥免疫抑制作用。有趣的是,CD8+ T细胞和Treg与不同组织病理特征相关:CD8+ T细胞与TIL密集相关(Pearson R=.498,P=.004),Treg则更多见于肿瘤芽生(TB)区域(Pearson R=.382,P=.029)。在独立的NAT前队列(n=95)中验证了这些观察结果:TIL密度较高,尤其是CD8+ T细胞增加、Treg减少,以及TB程度较低,均预测更好的NAT应答,并与总体及无病生存期改善相关。
这些发现为患者分层提供了重要依据,并凸显优化iCCA免疫靶向治疗的潜力。
Immunofluorescence analysis was conducted on a cohort of 34 resected iCCA cases to assess CD8+ T cell and Treg densities. Statistical correlations with survival and immune and histopathological features were examined. Validation was performed on an independent cohort of 95 iCCA pre-neoadjuvant therapy (NAT) biopsy specimens to assess the prognostic power of the immune and histopathological features to survival and NAT response.
In the cohort of resected iCCA cases, immunofluorescence revealed that increased CD8+ T-cell infiltration is associated with improved survival ( p = 0.018), underscoring their role in anti-tumor immunity. Conversely, higher density of Tregs is linked to poorer survival ( p = 0.038), suggesting its tumor-promoting, immunosuppressive effects. Intriguingly, CD8+ T cells and Tregs are associated with distinct histopathological features, with CD8+ T cells correlating with dense tumor-infiltrating lymphocytes (TILs, Pearson's R = 0.498; p = 0.004) and Tregs being more prevalent in regions of tumor budding (TB, Pearson's R = 0.382; p = 0.029). These observations were validated in an independent pre-NAT cohort ( n = 95), whereby higher TIL density, particularly increased CD8+ T cells and reduced Treg, and lower TB predict favorable response to NAT, as shown by improved overall and disease-free survival.
These findings provide critical insights for stratifying patients and highlight the potential for optimizing immune-targeted therapies in patients with iCCA.
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