CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Immunotherapy for the treatment of pediatric brain tumors: a narrative review.
Immunotherapy for the treatment of pediatric brain tumors: a narrative review.
本综述重点介绍了 20 篇已发表的文章,这些文章将免疫治疗用于儿童原发性脑肿瘤的治疗。
背景与目的:本文旨在综述已完成的儿童原发性中枢神经系统(CNS)肿瘤免疫治疗临床试验。CNS肿瘤是0–14岁儿童最常见的实体癌,也是儿童癌症死亡的首要原因。部分儿童脑肿瘤的生存率有所提高,但尽管治疗取得进展,仍有相当一部分患者结局不佳。癌症免疫治疗不断发展,在既往治疗应答不佳的儿童脑肿瘤中显示出前景。本文总结并讨论免疫治疗儿童脑肿瘤的已发表研究。方法:检索PubMed的MEDLINE、Elsevier的Embase和Scopus数据库,使用涵盖儿童、脑肿瘤和免疫疗法的关键词与主题词。纳入已完成的临床研究,治疗措施为任意免疫疗法,且原发性CNS肿瘤患者中至少一半为未满18岁的儿童;排除会议摘要及未报告完整安全性或主要结局结果的研究。主要内容与结果:检索得到1,494篇文献。标题和摘要筛选后,180篇进入全文评估,其中18篇纳入分析;另通过参考文献及新增发表文献补充纳入2篇,共20篇。所研究的免疫疗法包括树突状细胞疫苗、溶瘤病毒/病毒免疫疗法、嵌合抗原受体(CAR)T细胞疗法、肽疫苗、免疫调节药物等。结论:本文重点介绍了20篇采用免疫疗法治疗儿童原发性脑肿瘤的研究。截至目前,多数研究为I期或试点研究,主要评估安全性、最大耐受剂量和毒性,并监测生存结局。随着疗效和毒性特征逐渐明确,未来试验可进一步评估免疫治疗对儿童原发性脑肿瘤患者总生存期和生活质量的影响。
BACKGROUND AND OBJECTIVE: The goal of this narrative review is to report and summarize the completed pediatric immunotherapy clinical trials for primary CNS tumors. Pediatric central nervous system (CNS) tumors are the most common cause of pediatric solid cancer in children aged 0 to 14 years and the leading cause of cancer mortality. Survival rates for some pediatric brain tumors have improved, however, there remains a large portion of pediatric brain tumors with poor survival outcomes despite advances in treatment. Cancer immunotherapy is a growing field that has shown promise in the treatment of pediatric brain tumors that have historically shown a poor response to treatment. This narrative review provides a summary and discussion of the published literature focused on treating pediatric brain tumors with immunotherapy. METHODS: MEDLINE via PubMed, Embase and Scopus via Elsevier were searched. The search utilized a combination of keywords and subject headings to include pediatrics, brain tumors, and immunotherapies. Manuscripts included in the analysis included completed clinical studies using any immunotherapy intervention with a patient population that consisted of at least half pediatric patients (<18 years) with primary CNS tumors. Conference abstracts were excluded as well as studies that did not include completed safety or primary outcome results. KEY CONTENT AND FINDINGS: Search results returned 1,494 articles. Screening titles and abstracts resulted in 180 articles for full text review. Of the 180 articles, 18 were included for analysis. Another two articles were ultimately included after review of references and inclusion of newly published articles, for a total of 20 included articles. Immunotherapies included dendritic cell vaccines, oncolytic virotherapy/viral immunotherapy, chimeric antigen receptor (CAR) T-cell therapy, peptide vaccines, immunomodulatory agents, and others. CONCLUSIONS: In this review, 20 published articles were highlighted which use immunotherapy in the treatment of primary pediatric brain tumors. To date, most of the studies published utilizing immunotherapy were phase I and pilot studies focused primarily on establishing safety and maximum dose-tolerance and toxicity while monitoring survival endpoints. With established efficacy and toxicity profiles, future trials may progress to further understanding the overall survival and quality of life benefits to pediatric patients with primary brain tumors.
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