CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
不同的细胞因子调控诱导多能干细胞再生的 CD8(+) T 细胞的基因表达和抗肿瘤活性
英文原题：Distinct cytokines regulate gene expression and anti-tumor activity in regenerated CD8(+) T cells from induced pluripotent stem cells.
查看英文原题
Distinct cytokines regulate gene expression and anti-tumor activity in regenerated CD8(+) T cells from induced pluripotent stem cells.
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中文摘要
过继性T细胞疗法可诱导癌症患者的肿瘤消退。由诱导多能干细胞（iPSCs）再生而来的肿瘤特异性CD8+ T细胞，称为再生细胞毒性T淋巴细胞（CTLs），是过继性T细胞疗法的有前景的资源。然而，关于增强再生CTLs抗肿瘤活性的细胞因子知之甚少。在本研究中，我们检测了外源性细胞因子对再生CTLs的影响。我们发现IL-15和IL-21处理增强了再生CTLs的抗肿瘤活性，且这些细胞显示出不同的基因表达谱。经IL-15处理的再生CTLs表现出早期效应样特征，而经IL-21处理的再生CTLs则同时表现出初始样和效应样特征。此外，我们研究了细胞因子转导对再生CTLs的影响。IL-2、IL-7或IL-15转导，而非IL-21转导，增强了再生CTLs的存活和细胞毒性活性。重要的是，IL-7转导改善了再生CTLs在体内的抗肿瘤活性。这些发现为再生CTLs的临床应用提供了见解。
展开英文摘要原文
Adoptive T cell therapy can induce tumor regression in cancer patients. Tumor-specific CD8 + T cells regenerated from induced pluripotent stem cells (iPSCs), termed regenerated cytotoxic T lymphocytes (CTLs), are promising resources for adoptive T cell therapy.
However, little is known about the cytokines that enhance anti-tumor activity of regenerated CTLs. In this study, we examined effects of exogenous cytokines on regenerated CTLs.
We found that IL-15 and IL-21 treatment enhanced the anti-tumor activity of regenerated CTLs, and these cells showed distinct gene expression profiles. IL-15-treated regenerated CTLs exhibited early-effector-like characteristics, whereas IL-21-treated regenerated CTLs exhibited both naive- and effector-like characteristics.
Furthermore, we investigated effects of cytokine transduction on regenerated CTLs. IL-2, IL-7, or IL-15 transduction, but not IL-21 transduction, enhanced the survival and cytotoxic activity of regenerated CTLs.
Importantly, IL-7 transduction improved the anti-tumor activity of regenerated CTLs in vivo .
These findings provide insights for the clinical application of regenerated CTLs.
论文信息
- 作者
- Kondo K、Nitta N、Terada K、Sano Y、Kumode M、Nagano S、Masuda K、Okuzaki D
- 单位
- Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.Japan
- 期刊
- iScience2026 May 15
- 原文标识
- PubMed 42100743 · DOI 10.1016/j.isci.2026.115756
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