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:Diverse approaches and sources to derive antitumor T cell for liver cancer: a single-cell sequence based research.
Diverse approaches and sources to derive antitumor T cell for liver cancer: a single-cell sequence based research.
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比较了多种抗肿瘤 T 细胞诱导方法和来源,揭示了多种有效的抗肿瘤 T 细胞衍生方案,可作为肝癌 ACT 的来源。
尽管过继性细胞疗法(ACT)在血液肿瘤中取得了进展,但其在实体瘤中的作用仍不尽如人意,尤其是在原发性肝癌(PLC)中。因此,需要进一步研究PLC潜在的ACT来源。
初治原发性肝癌患者被前瞻性纳入本研究。手术期间获取肿瘤组织、淋巴结和血液样本。采用两种不同的抗原特异性T细胞诱导方法从PBMCs中形成细胞毒性T细胞群,并衍生出来自肿瘤组织联合TDLNs的抗肿瘤T细胞。使用单细胞RNA测序结合T细胞受体测序,基于不同抗肿瘤T细胞诱导方法和来源的分子及功能特性来鉴定细胞亚群。
本研究纳入了3例原发性肝癌患者。从临床样本中分离出19个簇共79,300个细胞转录组。经过两种不同的诱导方法后,CTL组和CTL2组均出现了免疫细胞的大量扩增,T细胞亚型高度一致,并且在这两组中均检测到抗肿瘤T细胞克隆的选择性扩增。基于增殖评分、效应评分和细胞因子表达的三方面比较表明,mRNA方法的免疫学效果与多抗原肽方法相当。最后,在CTL、CTL2和TAL-T细胞中发现的抗原特异性扩增T细胞克隆表明,肿瘤联合淋巴结可作为ACT的来源。
Primary liver cancer patients who had not previously received treatment were prospectively enrolled in this research. Tumor tissues combined with lymph node and blood samples were acquired during surgery. Two different antigen-specific T-cell induction approaches were used to form cytotoxic T-cell groups from PBMCs, and antitumor T cells from tumor tissues combined with TDLNs were derived. A single-cell RNA sequence coupled with a T-cell receptor sequence was used to identify the cell subsets based on the molecular and functional properties of diverse antitumor T-cell induction approaches and sources.
Three primary liver cancer patients were included in the present study. A total of 79,300 cell transcriptomes in 19 clusters were isolated from the clinical samples. After two different induction approaches, substantial amplification of immune cells occurred in both the CTL and CTL2 groups, with highly consistent T-cell subtypes, and selective amplification of antitumor T-cell clones in the two groups was also detected. The three-aspect comparison, which was based on the proliferation score, effect score and cytokine expression, indicated that the immunological effect of the mRNA approach was comparable to that of the multiantigen peptide approach. Finally, the antigen-specific expanded T-cell clones found in CTL, CTL2 and TAL-T cells indicated the potential of tumors combined with lymph nodes as sources for ACT.
Diverse antitumor T-cell induction approaches and sources were compared, revealing multiple effective options for antitumor T-cell derivation as a source of ACT for liver cancer.
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