双属性免疫细胞具有细胞毒性 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。双属性细胞类型，例如不变的自然杀伤 T 细胞、诱导 T 至 NK 细胞和细胞因子诱导的杀伤细胞，已在临床前和临床研究中证明了有效性和安全性。然而，它们的有限可用性阻碍了它们的广泛应用。人类多能干细胞 (hPSC) 提供了理想的来源。在这里，我们从 hPSC 中产生双属性诱导 T-NK (iTNK) 细胞，表达细胞毒性 T 细胞和 NK 细胞的标记物。单细胞 RNA 和 T 细胞受体 (TCR) 测序分析表明，iTNK 细胞表达与 NK 和 T 细胞相关的特征基因，并表现出多样化的 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，并抑制体内肿瘤生长。通过利用适应性和先天免疫反应，hPSC 衍生的 iTNK 细胞为癌症免疫治疗提供了有前途的策略。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

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.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.