肿瘤细胞治疗研究
英文原题：Facing CAR T Cell Challenges on the Deadliest Paediatric Brain Tumours.
中枢神经系统（CNS）肿瘤占儿童癌症诊断的25%，是儿童癌症相关死亡的主要原因。
中枢神经系统（CNS）肿瘤占儿童癌症诊断的25%，是儿童癌症相关死亡的主要原因。目前针对儿童CNS肿瘤的治疗远非最优，对于复发或难治性患者治疗失败。此外，发育中大脑的长期后遗症使得必须寻找新的创新方法。CAR-T 细胞（CAR T）疗法提高了B细胞恶性肿瘤患者的生存率，但CNS肿瘤的内在生物学特征阻碍了其成功。肿瘤的位置、异质性抗原表达、T细胞向肿瘤的有限浸润、血脑屏障提供的选择性转运以及免疫抑制性肿瘤微环境，已成为CAR T细胞疗法成功所需克服的主要障碍。在这篇综述中，我们将主要关注最致命的儿童高级别CNS肿瘤（髓母细胞瘤、室管膜瘤和高级别胶质瘤）的特征，以及CAR T细胞疗法提高生存率和患者生活质量的潜力。
Central nervous system (CNS) tumours comprise 25% of the paediatric cancer diagnoses and are the leading cause of cancer-related death in children. Current treatments for paediatric CNS tumours are far from optimal and fail for those that relapsed or are refractory to treatment. Besides, long-term sequelae in the developing brain make it mandatory to find new innovative approaches. Chimeric antigen receptor T cell (CAR T) therapy has increased survival in patients with B-cell malignancies, but the intrinsic biological characteristics of CNS tumours hamper their success. The location, heterogeneous antigen expression, limited infiltration of T cells into the tumour, the selective trafficking provided by the blood-brain barrier, and the immunosuppressive tumour microenvironment have emerged as the main hurdles that need to be overcome for the success of CAR T cell therapy. In this review, we will focus mainly on the characteristics of the deadliest high-grade CNS paediatric tumours (medulloblastoma, ependymoma, and high-grade gliomas) and the potential of CAR T cell therapy to increase survival and patients' quality of life.
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