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HLA 分子:CAR-T 细胞治疗的又一挑战

英文原题:HLA molecules: Another challenge for CAR T cell therapy.

查看英文原题

HLA molecules: Another challenge for CAR T cell therapy.

PubMed 2025/10/10(内容时间) Curr Res Transl Med Q3 · IF 3(JCR 2025)

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中文摘要

CAR-T 细胞疗法是血液系统恶性肿瘤治疗的一项突破性进展,有望诱导持久缓解。然而,抗原丢失、免疫逃逸和不利的肿瘤微环境等因素限制了疗效。CAR-T 疗法与HLA分子(尤其是HLA-DR和HLA-G)之间的相互作用,凸显了实现持续治疗成功的关键挑战。HLA-DR表达低或阴性的单核细胞以及HLA-G高表达,会促进免疫逃逸并降低CAR-T 疗效。此外,HLA遗传变异会影响血液系统恶性肿瘤易感性和疾病进展。调节HLA表达和功能的治疗策略对于克服这些障碍至关重要。阻断HLA-G、增强HLA-DR表达,以及通过基因编辑优化患者HLA特征等方法,有望改善CAR-T 治疗结局。持续研究HLA介导的免疫调节,将有助于改进这些策略并推动CAR-T 疗法发展。

展开英文摘要原文

CAR-T cell therapy marks a groundbreaking advancement in the treatment of hematological malignancies, demonstrating significant potential to induce durable remissions.

However, several limitations hinder its effectiveness, including antigen loss, immune evasion, and hostile tumor microenvironment. The interplay between CAR-T cell therapy and HLA molecules, particularly HLA-DR and HLA-G, emphasises critical challenges to achieving sustained therapeutic success. Monocytes with low or negative HLA-DR expression and high HLA-G presence contribute to immune evasion and reduced CAR-T cell effectiveness.

Additionally, genetic variations in HLA influence susceptibility to hematological malignancies and disease progression. Therapeutic strategies to regulate HLA expression and function are crucial to overcome these obstacles. Approaches such as blocking HLA-G, enhancing HLA-DR expression, and optimising HLA profiles in patients by gene editing can improve outcomes of CAR-T cell therapy. Continued research on HLA-mediated immune modulation will improve these strategies and advance CAR-T cell therapy.

论文信息

作者
Salih I、Fakhkhari M、Berrougui H、Khalil A、Benabdellah K、Atilla E、Sadki K
第一作者单位
Research Laboratory in Oral Biology and Biotechnology, Faculty of Dental Medicine, Mohammed V University in Rabat, Rabat, Morocco; Department of Medicine, Geriatric Service, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 4N4, Canada.Canada
通讯作者单位
Research Laboratory in Oral Biology and Biotechnology, Faculty of Dental Medicine, Mohammed V University in Rabat, Rabat, Morocco. Electronic address: k.sadki@um5r.ac.ma.
文献类型
综述
期刊
Current research in translational medicine2025 Dec
原文标识
PubMed 41086595 · DOI 10.1016/j.retram.2025.103547