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放疗联合 CAR-T 细胞治疗的现状:对谨慎乐观的注解?

英文原题:Radiotherapy plus CAR-T cell therapy to date: A note for cautions optimism?

查看英文原题

Radiotherapy plus CAR-T cell therapy to date: A note for cautions optimism?

PubMed 2022/11/17(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

放疗(RT)是一种以电离辐射为核心的传统治疗方案,然而由于放射抵抗,RT在很大程度上仍属姑息性治疗。缺氧、免疫细胞的放射敏感性以及癌症干细胞(CSCs)等因素均参与影响受照射肿瘤微环境(TME)中放射抵抗的重要作用。由于恶性肿瘤治疗取得了重大进展,一种有前景的方法是利用基因修饰的嵌合抗原受体(CARs)T细胞来清除实体瘤。此外,靶向CSC相关标志物的CAR-T 细胞将能够清除放射抵抗的实体瘤。但支持免疫荒漠型TME的实体瘤被描述为免疫抑制性,通常对CAR-T 细胞治疗无应答。而RT可以克服这些免疫抑制特征;因此,越来越多的证据支持RT与CAR-T 细胞治疗的联合应用。在这篇综述中,我们深入探讨了放射抵抗机制、CAR-T 细胞在TME内应对实体瘤的进展与障碍。因此,我们重点关注如何利用联合策略来消除这些障碍。最后,我们展示了这种治疗组合所面临的挑战。

展开英文摘要原文

Radiotherapy (RT) is a traditional therapeutic regime that focuses on ionizing radiation, however, RT maintains largely palliative due to radioresistance. Factors such as hypoxia, the radiosensitivity of immune cells, and cancer stem cells (CSCs) all come into play in influencing the significant impact of radioresistance in the irradiated tumor microenvironment (TME).

Due to the substantial advances in the treatment of malignant tumors, a promising approach is the genetically modified T cells with chimeric antigen receptors (CARs) to eliminate solid tumors.

Moreover, CAR-T cells targeting CSC-related markers would eliminate radioresistant solid tumors.

But solid tumors that support an immune deserted TME, are described as immunosuppressive and typically fail to respond to CAR-T cell therapy. And RT could overcome these immunosuppressive features; thus, growing evidence supports the combination of RT with CAR-T cell therapy. In this review, we provide a deep insight into the radioresistance mechanisms, advances, and barriers of CAR-T cells in response to solid tumors within TME.

Therefore, we focus on how the combination strategy can be used to eliminate these barriers.

Finally, we show the challenges of this therapeutic partnership.

论文信息

作者
Huan T、Li H、Tang B
单位
Department of Rehabilitation Medicine, Jinhu County People's Hospital, Huaian, Jiangsu, China.China
文献类型
综述 · 非美国政府资助研究
期刊
Frontiers in immunology2022
原文标识
PubMed 36466874 · DOI 10.3389/fimmu.2022.1033512