RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Generation of dual-attribute iTNK cells from hPSCs for cancer immunotherapy.
Generation of dual-attribute iTNK cells from hPSCs for cancer immunotherapy.
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双属性免疫细胞具备细胞毒性T细胞和自然杀伤(NK)细胞的优势特征,有望推动免疫治疗的发展。恒定自然杀伤T细胞、诱导性T-to-NK细胞和细胞因子诱导的杀伤细胞等双属性细胞类型已在临床前和临床研究中展现出疗效和安全性。然而,其来源有限阻碍了广泛应用。人多能干细胞(hPSCs)提供了理想的来源。在此,我们从hPSCs中生成双属性诱导性T-NK(iTNK)细胞,其表达细胞毒性T细胞和NK细胞的标志物。单细胞RNA和T细胞受体(TCR)测序分析显示,iTNK细胞表达与NK细胞和T细胞相关的特征基因,并呈现多样化的TCR库。iTNK细胞释放细胞毒性介质,对多种肿瘤细胞系发挥细胞毒性作用,并在体内抑制肿瘤生长。通过利用适应性免疫和固有免疫应答,hPSC来源的iTNK细胞为癌症免疫治疗提供了有前景的策略。
Dual-attribute immune cells possess advantageous features of cytotoxic T cells and natural killer (NK) cells and hold promise for advancing immunotherapy. Dual-attribute cell types such as invariant natural killer T cells, induced T-to-NK cells, and cytokine-induced killer cells have demonstrated efficacy and safety in preclinical and clinical studies.
However, their limited availability hinders their widespread application. Human pluripotent stem cells (hPSCs) offer an ideal source.
Here, we generate dual-attribute induced T-NK (iTNK) cells from hPSCs, expressing markers of both cytotoxic T and NK cells. Single-cell RNA and T cell receptor (TCR) sequencing analyses reveal that iTNK cells expressed signature genes associated with both NK and T cells and displayed a diverse TCR repertoire.
iTNK cells release cytotoxic mediators, exert cytotoxicity against diverse tumor cell lines, and inhibit tumor growth in vivo. By harnessing adaptive and innate immune responses, hPSC-derived iTNK cells offer promising strategies for cancer immunotherapy.
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