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:The predictive value of tumor infiltrating leukocytes in Hepatocellular Carcinoma: A systematic review and meta-analysis.
The predictive value of tumor infiltrating leukocytes in Hepatocellular Carcinoma: A systematic review and meta-analysis.
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与其他实体瘤一样,免疫浸润对切除后的生存有很大影响。
肝细胞癌(HCC)患者通常只有通过切除或移植手术才有治愈机会。肝癌发生及术后预后不仅取决于肝硬化,也受免疫激活和耗竭影响,因此许多研究考察了肿瘤浸润白细胞(TIL)亚群。本系统综述和荟萃分析旨在描述相关细胞群,并评估其对总生存期(OS)、无病生存期(DFS)和无复发生存期(RFS)的预测能力。
系统检索PubMed数据库(PROSPERO 172324),收集截至2018年12月的CD3+、CD8+、Treg、B细胞、巨噬细胞、中性粒细胞和NK细胞数据及相关参考文献。通过随机效应荟萃分析,比较高、低浸润水平对应的OS、DFS和RFS。
共纳入20篇发表文献中的3541例患者。除Treg和中性粒细胞外,各研究间异质性中至高。CD3+、CD8+及NK细胞浸润较高预示更好的生存(OS、DFS和RFS;p<0.05)。Treg及中性粒细胞浸润较高则预示较低的OS和DFS。巨噬细胞和B细胞浸润与生存无显著差异。讨论:与其他实体瘤一样,免疫浸润显著影响切除术后的生存。不过,这些研究大多为回顾性研究,不能排除明显的发表偏倚。尽管如此,鉴于新型免疫调节疗法的发展,这些发现为有效且耐受性良好的辅助治疗开辟了新方向。
For Hepatocellular carcinoma (HCC) surgery either through resection or transplantation often provides the only chance for cure. Since hepatocarcinogenesis and postsurgical prognosis is not only dependent on cirrhosis but also on immune activation and exhaustion, many studies have investigated tumor infiltrating leukocyte (TIL) subsets. This systematic review and meta-analysis aims at describing the cell groups and their predictive power regarding overall (OS), disease free (DFS) and recurrence free survival (RFS). MATERIAL AND METHODS: A systematic search of the PubMed database was conducted (PROSPERO 172324). Data on CD3 + , CD8 + , Treg, B cells, macrophages, neutrophil and NK-cells were collected from Pubmed and related references up to December 2018. Overall (OS), disease-free (DFS) and recurrence free survival (RFS) in dependence of high vs. low infiltration rates were compared using a random effects meta-analysis.
Altogether data from 3541 patients enrolled in 20 publications were included. Except for Tregs and Neutrophils, heterogeneity analysis was found to be moderate to high across the studies. High CD3 + , CD8 + , NK-cell infiltration predicted better survival (OS, DFS and RFS; p < 0.05). Higher Treg and Neutrophil infiltration predicted lower OS and DFS. For Macrophages and B cells no difference in survival could be found. DISCUSSION: As with other solid tumors immune infiltration has a great influence on survival after resection. However, a considerable publication bias cannot be ruled out in mostly retrospective analyses. Nevertheless, in light of novel immune modulatory treatments this opens a new avenue towards effective and well-tolerated adjuvant treatment.
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