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:Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma.
Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma.
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hDIF 检测显示针对非 HBV/非 HCV 肝细胞癌的免疫反应存在明显差异,并揭示了向外周血的免疫抑制梯度。
肝移植和肝切除是早期肝细胞癌(HCC)的根治性治疗选择,治疗结局部分取决于机体对恶性肿瘤的免疫应答。本研究旨在确定非丙型肝炎病毒/非乙型肝炎病毒(非HCV/非HBV)HCC患者的免疫学特征。
采用多色流式细胞术测量39种免疫细胞亚群,并对10例接受HCC切除患者及10名健康供者的外周血(PB)和肿瘤组织进行免疫表型分析。采用多维方法分析高分辨白细胞分类计数(hDIF)特征,并通过细胞内IFN-γ染色评估功能(试验注册号DRKS00013567)。
hDIF显示抗肿瘤应答同时存在激活和抑制特征:T、B、NK及树突状细胞亚群被激活,而髓源性抑制细胞及调节性T、B细胞亚群具有抑制作用。对外周血和肿瘤浸润白细胞(TIL)的主成分分析显示存在抗肿瘤激活梯度。TIL能够分泌IFN-γ,显示具有功能活性,但未能杀伤HCC细胞。
hDIF测量显示非HBV/非HCV HCC中存在不同的免疫反应特征,并呈现向外周血方向增强的免疫抑制梯度。试验注册号:DRKS00013567。
Liver transplantation and liver resection are curative options for early hepatocellular carcinoma (HCC). The outcome is in part depended on the immunological response to the malignancy. In this study, we aimed to identify immunological profiles of non-HCV/non-HBV HCC patients.
Thirty-nine immune cell subsets were measured with multicolor flow cytometry. This immunophenotyping was performed in peripheral blood (PB) and tumor specimens of 10 HCC resection patients and 10 healthy donors. The signatures of the highly differential leukocyte count (hDIF) were analyzed using multidimensional techniques. Functional capability was measured using intracellular IFN- staining (Trial Registration DRKS00013567).
The hDIF showed activation (subsets of T-, B-, NK- and dendritic cells) and suppression (subsets of myeloid-derived suppressor cells and T- and B-regulatory cells) of the antitumor response. Principal component analysis of PB and tumor infiltrating leukocytes (TIL) illustrated an antitumor activating gradient. TILs showed functional capability by secreting IFN- but did not kill HCC cells.
In conclusion, the measurement of the hDIF shows distinct differences in immune reactions against non-HBV/non-HCV HCC and illustrates an immunosuppressive gradient toward peripheral blood. TRIAL REGISTRATION: DRKS00013567.
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