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用于增强过继性细胞治疗中免疫细胞运输的最佳趋化因子受体

英文原题:Optimal chemokine receptors for enhancing immune cell trafficking in adoptive cell therapy.

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Optimal chemokine receptors for enhancing immune cell trafficking in adoptive cell therapy.

PubMed 2025/01/16(内容时间) Immunol Res Q3 · IF 2.7(JCR 2025)

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中文摘要

最近,一种通过在免疫细胞上改造趋化因子受体的策略被开发出来,用于优化实体瘤的过继性细胞治疗(ACT)。鉴于不同肿瘤类型之间趋化因子分泌存在差异,识别并调控合适的趋化因子受体至关重要。

在本研究中,我们利用来自The Cancer Genome Atlas的肿瘤组织和来自Genotype-Tissue Expression的正常组织的大量RNA测序数据,研究趋化因子的表达谱。通过分析,我们鉴定出八种趋化因子受体,其在肿瘤组织中的趋化因子水平较正常组织升高,使其成为增强ACT的有前景候选者。随后对TIL(肿瘤浸润淋巴细胞)和嵌合抗原受体-T细胞的检查显示,八种候选趋化因子受体中有五种在T细胞中并未表现出表达升高。在五种候选者中,我们证明CXCR5是特别有前景的候选者,可在不损害细胞活力或细胞毒性的情况下增强细胞迁移。

总之,我们的研究强调了五种趋化因子受体(CCR6、CCR9、CXCR1、CXCR5和XCR1)作为调控ACT以增强细胞运输并可能改善癌症治疗结局的有价值靶点的潜力。

展开英文摘要原文

Recently, a strategy involving the engineering of chemokine receptors on immune cells was developed to optimize adoptive cell therapy (ACT) for solid tumors. Given the variability in chemokine secretion among different tumor types, identifying and modulating the appropriate chemokine receptors is crucial. In this study, we utilized extensive RNA sequencing data from both tumor tissues from The Cancer Genome Atlas and normal tissues from Genotype-Tissue Expression to investigate the expression profiles of chemokines.

Through analysis, we identified eight chemokine receptors associated with increased chemokine levels in tumor tissues compared to normal tissues, making them promising candidates for enhancing ACT.

Subsequent examination of tumor-infiltrating lymphocytes and chimeric antigen receptor-T cells revealed that five out of the eight candidate chemokine receptors did not exhibit elevated expression in T cells. Among five candidates, we demonstrated that CXCR5 is a particularly promising candidate for enhancing cell migration without compromising cell viability or cytotoxicity.

In conclusion, our study underscores the potential of five chemokine receptors (CCR6, CCR9, CXCR1, CXCR5, and XCR1) as valuable targets for modulating ACT to enhance cell trafficking and potentially improve cancer therapy outcomes.

论文信息

作者
Han D、Jeong BK、Hong JM、Seo JH、Lee G、Kim K、Hong C、Lee H
第一作者单位
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro, 43-Gil, Songpa-Gu, Seoul, 05505, Korea.South Korea
通讯作者单位
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro, 43-Gil, Songpa-Gu, Seoul, 05505, Korea. backlila@gmail.com.South Korea
期刊
Immunologic research2025 Jan 16
原文标识
PubMed 39815137 · DOI 10.1007/s12026-024-09560-y