改变的癌症代谢和对下一代 CAR T 细胞疗法的影响。
Altered cancer metabolism and implications for next-generation CAR T-cell therapies.
机构信息
Brain Tumor Immunotherapy Laboratory, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Medical Scientist Training Program, School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
出版信息
Pharmacol Ther. 2024 Jul;259:108667. doi: 10.1016/j.pharmthera.2024.108667. Epub 2024 May 17.
This review critically examines the evolving landscape of chimeric antigen receptor (CAR) T-cell therapy in treating solid tumors, with a particular focus on the metabolic challenges within the tumor microenvironment. CAR T-cell therapy has demonstrated remarkable success in hematologic malignancies, yet its efficacy in solid tumors remains limited. A significant barrier is the hostile milieu of the tumor microenvironment, which impairs CAR T-cell survival and function. This review delves into the metabolic adaptations of cancer cells and their impact on immune cells, highlighting the competition for nutrients and the accumulation of immunosuppressive metabolites. It also explores emerging strategies to enhance CAR T-cell metabolic fitness and persistence, including genetic engineering and metabolic reprogramming. An integrated approach, combining metabolic interventions with CAR T-cell therapy, has the potential to overcome these constraints and improve therapeutic outcomes in solid tumors.
这篇综述批判性地考察了嵌合抗原受体（CAR）T 细胞疗法在治疗实体瘤方面的不断发展的领域，特别关注肿瘤微环境中的代谢挑战。CAR T 细胞疗法在血液恶性肿瘤方面已经取得了显著的成功，但在实体瘤中的疗效仍然有限。一个重要的障碍是肿瘤微环境的恶劣环境，这会损害 CAR T 细胞的存活和功能。本综述深入探讨了癌细胞的代谢适应及其对免疫细胞的影响，强调了对营养物质的竞争和免疫抑制代谢物的积累。它还探讨了增强 CAR T 细胞代谢适应性和持久性的新兴策略，包括基因工程和代谢重编程。将代谢干预与 CAR T 细胞疗法相结合的综合方法有可能克服这些限制，提高实体瘤的治疗效果。
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