Lower Silesian Centre of Oncology, Pulmonology and Hematology, Wroclaw 53-413, Poland; Medical University Hospital, Borowska 213, Wrocław 50-556, Poland.
Lower Silesian Centre of Oncology, Pulmonology and Hematology, Wroclaw 53-413, Poland; Department of Oncology, Wroclaw Medical University, Wroclaw 50-367, Poland.
Biomed Pharmacother. 2024 May;174:116532. doi: 10.1016/j.biopha.2024.116532. Epub 2024 Apr 3.
Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells. This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide. We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors. Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes. In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment.
嵌合抗原受体 T (CAR-T) 细胞疗法是一种开创性的免疫疗法。然而,它在治疗实体瘤方面面临着巨大的挑战,需要解决诸如不良运输、有限渗透和在肿瘤微环境 (TME) 中不足的持久性等问题。CAR-T 细胞经过工程改造,表达靶向特定癌症抗原的受体,增强其识别和消除癌细胞的能力。这篇综述文章探讨了 CAR-T 疗法与放射治疗 (RT) 之间的复杂相互作用,研究了它们的协同潜力。放射治疗是一种标准的癌症治疗方法,涉及使用高剂量的辐射来靶向和破坏癌细胞,从而破坏其生长和分裂的能力。我们强调 RT 调节 TME,增强抗原呈递,并促进免疫细胞浸润,从而增强 CAR-T 细胞介导的肿瘤清除。分子研究揭示了 RT 诱导的肿瘤基质改变、T 细胞募集促进和免疫原性细胞死亡的诱导作用。值得注意的是,联合低分割放疗和髓系来源抑制细胞阻断等策略突显了增强实体瘤中 CAR-T 细胞疗法的创新方法。讨论了 RT 和 CAR-T 细胞在血液恶性肿瘤中的联合适应症,强调了 RT 策略性增强 CAR-T 细胞疗效的情况。本文批判性地评估了 RT 作为桥梁与传统化疗相比的作用,强调了为优化 CAR-T 治疗结果而进行的时间和剂量考虑的重要性。总之,本文深入了解了 RT 激活的复杂分子机制和创新策略,以改善 CAR-T 细胞疗法,为它们在癌症治疗中的联合应用提供了有价值的见解。
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