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增强过继性细胞治疗:神经肿瘤学中免疫细胞辐射防护的未来策略

英文原题:Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncology.

查看英文原题

Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncology.

PubMed 2025/07/29(内容时间) NPJ Precis Oncol Q1 · IF 9.9(JCR 2025)

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中文摘要

过继性细胞疗法(ACT),尤其是CAR-T 细胞疗法,已成为癌症治疗中一种有前景的方法,在血液系统恶性肿瘤中显示出疗效,但在脑肿瘤中面临挑战。ACT与放射治疗(RT)的联合提供了一种潜在策略以增强治疗效果,因为RT可通过促进抗原呈递和T细胞募集来刺激免疫反应。然而,一个主要障碍是免疫细胞的放射敏感性,导致其在辐射野内迅速耗竭,从而削弱了这种联合治疗的益处。本综述探讨了提高免疫细胞放射抗性的策略,强调了创新性放射防护方法的必要性。我们讨论了极端微生物来源分子的潜力,例如来自缓步动物的损伤抑制蛋白,作为新型放射防护剂可整合到ACT方案中。此外,我们阐述了临床试验设计的关键考虑因素,包括RT与ACT的序贯安排、剂量参数和安全性考虑。通过桥接极端微生物生物学与免疫肿瘤学的见解,本工作旨在优化ACT在脑肿瘤这一具有挑战性的背景下的疗效,为神经肿瘤学中增强治疗策略铺平道路。

展开英文摘要原文

Adoptive cell therapy (ACT), particularly chimeric antigen receptor T cell (CAR T) therapy, has emerged as a promising approach in cancer treatment, demonstrating efficacy in hematological malignancies but facing challenges in brain tumors. The combination of ACT with radiation therapy (RT) offers a potential strategy to enhance therapeutic outcomes, as RT can stimulate immune responses by promoting antigen presentation and T cell recruitment.

However, a major hurdle is the radiosensitivity of immune cells, leading to their rapid depletion within the radiation field, which undermines the benefits of this combination. This review explores strategies to increase the radioresistance of immune cells, highlighting the need for innovative radioprotective approaches.

We discuss the potential of extremophile-derived molecules, such as the Damage Suppressor protein from tardigrades, as novel radioprotectants that could be integrated into ACT protocols.

Furthermore, we address key considerations for clinical trial design, including the sequencing of RT and ACT, dosing parameters, and safety considerations. By bridging insights from extremophile biology and immuno-oncology, this work aims to optimize the efficacy of ACT in the challenging context of brain tumors, paving the way for enhanced treatment strategies in neuro-oncology.

论文信息

作者
Groth AJ、Khasraw M、Byrne JD、Reitman ZJ
第一作者单位
Department of Radiation Oncology, Duke University School of Medicine, Durham, NC, USA.United States
通讯作者单位
Department of Radiation Oncology, Duke University School of Medicine, Durham, NC, USA. zjr@duke.edu.United States
文献类型
综述
期刊
NPJ precision oncology2025 Jul 29
原文标识
PubMed 40730675 · DOI 10.1038/s41698-025-01059-5