通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
我们的研究结果定义了一个精准溶瘤平台,该平台能够解除TAM介导的免疫抑制,同时增强适应性免疫,为癌症免疫治疗提供了一条有前景的转化途径。
英文原题:Immunotherapy-related neurotoxicity in the central nervous system of children with cancer.
Immunotherapy-related neurotoxicity in the central nervous system of children with cancer.
我们对儿童患者免疫治疗相关神经毒性的理解仍存在显著空白,很大程度上是因为我们的知识大多来自成人研究。
我们对儿童患者免疫治疗相关神经毒性的理解仍存在显著空白,很大程度上是因为我们的知识大多来自成人研究。由于术语和分级系统的差异,准确识别儿童免疫治疗的不良反应也具有挑战性。此外,免疫治疗相关神经毒性的表现因不同疾病、各种治疗方式、剂量和给药方法而差异很大。将免疫治疗与其他治疗相结合可能改善结局,但会带来新的复杂性以及毒性增加的可能性。此外,与颅外恶性肿瘤的儿童患者相比,颅内恶性肿瘤的儿童患者对免疫治疗有独特的反应和不同的神经毒性。因此,我们必须加深对这一脆弱群体中免疫治疗神经毒性作用的病理生理学、患病率、严重程度和管理的理解。本综述整合了当前关于儿童肿瘤学中免疫治疗相关神经毒性的知识,重点介绍了多种类型的神经毒性,包括细胞因子释放综合征(CRS)、免疫效应细胞相关神经毒性综合征(ICANS)和肿瘤炎症相关神经毒性(TIAN)等。此外,我们还探讨了与过继性细胞治疗(ACT)、抗体类疗法、免疫检查点抑制剂(ICIs)、溶瘤病毒(OV)和癌症疫苗相关的神经毒性的独特特征。
Significant gaps remain in our understanding of immunotherapy-related neurotoxicity in pediatric patients, largely because much of our knowledge comes from studies in adults. Accurately identifying the adverse effects of immunotherapy in children is also challenging, owing to variations in terminology and grading systems. Moreover, the manifestation of immunotherapy-related neurotoxicity differs greatly across different diseases, various modalities, dosages, and delivery methods. Combining immunotherapy with other treatments might improve outcomes but introduces new complexities and potential for increased toxicities. Additionally, pediatric patients with intracranial malignancy have unique responses to immunotherapies and distinct neurotoxicity compared to those with extracranial malignancy. Consequently, we must enhance our understanding of the pathophysiology, prevalence, severity, and management of immunotherapy's neurotoxic effects in this vulnerable group. This review consolidates the current knowledge of immunotherapy-related neurotoxicity in pediatric oncology, highlighting various types of neurotoxicity including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and tumor inflammation-associated neurotoxicity (TIAN), among others. Furthermore, we examine the unique features of neurotoxicity associated with adoptive cellular therapy (ACT), antibody-based therapies, immune checkpoint inhibitors (ICIs), oncolytic viruses (OV), and cancer vaccines.
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