Optogenetic control of T cells for immunomodulation.

IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Brendan McKee, Siyao Liu, Pauline X Cai, Zimo Yang, Tien-Hung Lan, Yubin Zhou
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引用次数: 0

Abstract

Cellular immunotherapy has transformed cancer treatment by harnessing T cells to target malignant cells. However, its broader adoption is hindered by challenges such as efficacy loss, limited persistence, tumor heterogeneity, an immunosuppressive tumor microenvironment (TME), and safety concerns related to systemic adverse effects. Optogenetics, a technology that uses light-sensitive proteins to regulate cellular functions with high spatial and temporal accuracy, offers a potential solution to overcome these issues. By enabling targeted modulation of T cell receptor signaling, ion channels, transcriptional programming, and antigen recognition, optogenetics provides dynamic control over T cell activation, cytokine production, and cytotoxic responses. Moreover, optogenetic strategies can be applied to remodel the TME by selectively activating immune responses or inducing targeted immune cell depletion, thereby enhancing T cell infiltration and immune surveillance. However, practical hurdles such as limited tissue penetration of visible light and the need for cell- or tissue-specific gene delivery must be addressed for clinical translation. Emerging solutions, including upconversion nanoparticles, are being explored to improve light delivery to deeper tissues. Future integration of optogenetics with existing immunotherapies, such as checkpoint blockade and adoptive T cell therapies, could improve treatment specificity, minimize adverse effects, and provide real-time control over immune responses. By refining the precision and adaptability of immunotherapy, optogenetics promises to further enhance both the safety and efficacy of cancer immunotherapy.

T细胞免疫调节的光遗传学控制。
细胞免疫疗法通过利用T细胞靶向恶性细胞改变了癌症治疗。然而,其广泛采用受到诸如疗效丧失、有限的持久性、肿瘤异质性、免疫抑制肿瘤微环境(TME)以及与全身不良反应相关的安全性问题等挑战的阻碍。光遗传学是一种利用光敏蛋白以高空间和时间精度调节细胞功能的技术,为克服这些问题提供了一个潜在的解决方案。通过靶向调节T细胞受体信号、离子通道、转录编程和抗原识别,光遗传学提供了对T细胞活化、细胞因子产生和细胞毒性反应的动态控制。此外,光遗传学策略可以通过选择性激活免疫应答或诱导靶向免疫细胞消耗来重塑TME,从而增强T细胞浸润和免疫监视。然而,实际的障碍,如有限的可见光穿透组织和需要细胞或组织特异性基因传递必须解决临床翻译。新兴的解决方案,包括上转换纳米粒子,正在被探索,以改善光传输到更深的组织。未来将光遗传学与现有的免疫疗法(如检查点阻断和过继T细胞疗法)结合起来,可以提高治疗特异性,最大限度地减少不良反应,并提供对免疫反应的实时控制。通过提高免疫治疗的精确性和适应性,光遗传学有望进一步提高癌症免疫治疗的安全性和有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Essays in biochemistry
Essays in biochemistry 生物-生化与分子生物学
CiteScore
10.50
自引率
0.00%
发文量
105
审稿时长
>12 weeks
期刊介绍: Essays in Biochemistry publishes short, digestible reviews from experts highlighting recent key topics in biochemistry and the molecular biosciences. Written to be accessible for those not yet immersed in the subject, each article is an up-to-date, self-contained summary of the topic. Bridging the gap between the latest research and established textbooks, Essays in Biochemistry will tell you what you need to know to begin exploring the field, as each article includes the top take-home messages as summary points. Each issue of the journal is guest edited by a key opinion leader in the area, and whether you are continuing your studies or moving into a new research area, the Journal gives a complete picture in one place. Essays in Biochemistry is proud to publish Understanding Biochemistry, an essential online resource for post-16 students, teachers and undergraduates. Providing up-to-date overviews of key concepts in biochemistry and the molecular biosciences, the Understanding Biochemistry issues of Essays in Biochemistry are published annually in October.
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