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:Pathological study of the tumor microenvironment after neoadjuvant therapy in hepatocellular carcinoma: Difference of TACE combined with antiangiogenics and immunotherapy.
Pathological study of the tumor microenvironment after neoadjuvant therapy in hepatocellular carcinoma: Difference of TACE combined with antiangiogenics and immunotherapy.
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癌组织中 CD8+TILs 的病理学评估可作为评价 HCC 新辅助治疗疗效的重要指标。
肝细胞癌(HCC)是全球最常见的原发性肝癌。经导管动脉化疗栓塞(T)常用于治疗不可切除肿瘤。T联合抗血管生成治疗和免疫治疗(AI)在新辅助治疗中取得显著进展,但其机制尚不明确。本研究旨在从病理学角度探究HCC中T+AI提高疗效的原因。
回顾性分析49例接受术前T治疗后进行手术切除的HCC患者。其中23例接受T+AI,26例仅接受T。通过免疫组织化学评估临床数据,包括无病生存期。采用4种方法记录免疫细胞,包括TIL(肿瘤浸润淋巴细胞)比例(肿瘤中心区域阳性淋巴细胞所占比例)及其他3种指标。根据血管是否呈现包裹肿瘤细胞簇的血管包绕肿瘤簇(VETC)模式进行分类。
组间分析提示,T+AI组无病生存期显著优于T组。分析显示,CD8+ TIL是新辅助治疗结局的预后因素;T+AI组碳酸酐酶9和VETC阳性率较低,免疫细胞浸润和血管分类存在显著差异。VETC阳性与较高残余肿瘤率及较低CD8+ TIL水平相关。
评估肿瘤组织中的CD8+ TIL可能是判断HCC新辅助治疗疗效的重要指标。VETC和碳酸酐酶9的存在也可能影响新辅助治疗疗效,并有望作为相关指标。
HCC is the leading form of primary liver cancer worldwide. Transcatheter arterial chemoembolization (T) is commonly used to treat unresectable tumors. T combined with antiangiogenic therapy and immunotherapy (AI) has shown significant progress in neoadjuvant treatment, although the underlying mechanisms remain unclear. This study aimed to explore the reasons for the enhanced efficacy of T+AI from a pathological perspective in the context of HCC.
A retrospective analysis was conducted on 49 patients with HCC who were treated with T before surgical resection. Twenty-three patients received T+AI, while 26 received only T. Immunohistochemistry was performed to evaluate clinical data, including disease-free survival. Immune cells were recorded based on 4 methods, including tumor-infiltrating lymphocyte (TIL) percentage (the percentage of positive lymphocytes in the central area of the tumor) and the other 3 methods. Blood vessels were classified on the basis of the presence of VETC (vessels that encapsulate tumor clusters).
The group analysis results suggested that disease-free survival in the T+AI group was significantly better than that in the T group. Analysis revealed that CD8+TILs were a prognostic factor for neoadjuvant treatment and lower carbonic anhydrase 9 and VETC positivity in the T+AI group, with significant differences in immune cell infiltration and vascular classification. VETC positivity was associated with higher residual tumor rates and lower CD8+TIL levels.
Pathological assessment of CD8+TILs in cancer tissues may serve as an important indicator for evaluating the efficacy of neoadjuvant therapy in HCC. The presence of VETC and carbonic anhydrase 9 may also affect the efficacy of neoadjuvant therapy and could potentially serve as indicators.
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