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?
英文原题:Clinicopathologic features and tumor immune microenvironment of lymphocyte-rich hepatocellular carcinoma.
Clinicopathologic features and tumor immune microenvironment of lymphocyte-rich hepatocellular carcinoma.
富淋巴细胞性肝细胞癌(LR-HCC)是一种罕见的HCC变异型,以显著的淋巴细胞浸润为特征,为探索肿瘤免疫微环境(TIME)及其对疾病进展和治疗的潜在影响提供了机会。
富含淋巴细胞的肝细胞癌(LR-HCC)是HCC的一种罕见变异型,以显著的淋巴浸润为特征,为探索肿瘤免疫微环境(TIME)及其对疾病进展和治疗的潜在影响提供了机会。本研究旨在描述LR-HCC的临床病理特征和TIME组分,以指导更有效的治疗策略。在本研究中,我们呈现了五例新的LR-HCC病例,并对136例既往文献报道的病例进行了全面回顾性分析。采用免疫组化评估系统性地评价TIME组分和免疫检查点抑制剂(ICI)靶点。我们的研究结果显示,CD3+ T细胞显著多于CD20+ B细胞(1.5:1,P < 0.001),且CD8+细胞毒性T细胞的比例高于Foxp3+调节性T细胞(2.4:1,P < 0.001),提示该免疫格局可能有利于免疫治疗干预。使用VENTANA SP263检测法在五例中的三例中检测到程序性细胞死亡配体1(PD-L1)表达,提示对ICI可能存在应答。对38例病例的汇总分析显示,5年总生存率为73.6%,明显低于既往报道的比率(>90%),其中29.4%的患者出现术后复发或淋巴结转移。多因素分析确定肿瘤大小为总生存的独立预测因子。这些发现强调了TIME特征在理解LR-HCC中的相关性,并指出了靶向治疗和免疫治疗的前景,有助于优化这一独特癌症亚型的临床管理。
Lymphocyte-rich hepatocellular carcinoma (LR-HCC) is a rare variant of HCC characterized by pronounced lymphoid infiltration, providing an opportunity to explore the tumor immune microenvironment (TIME) and its potential impact on disease progression and therapy. This study aimed to describe the clinicopathological features and TIME components of LR-HCC to inform more effective treatment strategies. In this study, we present five novel cases of LR-HCC alongside a comprehensive retrospective analysis of 136 previously documented cases. Immunohistochemical evaluation was utilized to systematically assess TIME components and immune checkpoint inhibitor (ICI) targets. Our findings demonstrated a significant predominance of CD3+ T cells over CD20+ B cells (1.5:1, P < 0.001) and a higher frequency of CD8+ cytotoxic T cells compared to Foxp3+ regulatory T cells (2.4:1, P < 0.001), indicating an immune landscape potentially favorable for immunotherapeutic interventions. Programmed cell death ligand 1 (PD-L1) expression was detected in three out of five cases using the VENTANA SP263 assay, suggesting potential responsiveness to ICIs. A pooled analysis of 38 cases showed a 5-year overall survival rate of 73.6 %, which is notably lower than previously reported rates (>90 %), with 29.4 % of patients experiencing postoperative recurrence or lymph node metastasis. Multivariate analysis identified tumor size as an independent predictor of overall survival. These findings emphasize the relevance of TIME characteristics in understanding LR-HCC and point to promising avenues for targeted and immune-based therapies, contributing to the optimization of clinical management for this distinct cancer subtype.
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