研究概要
尽管将抗GD2免疫治疗纳入标准治疗已改善了预后,但高危患者的五年生存率仍低于50%。
中文摘要
神经母细胞瘤是最常见的颅外儿童实体瘤。尽管将抗GD2免疫治疗纳入标准治疗已改善预后,但高危患者的五年生存率仍低于50%。这凸显出,虽然免疫治疗在这种儿童癌症中具有前景,但神经母细胞瘤已发展出多种免疫抑制机制,限制抗肿瘤免疫应答。其中,髓系细胞,包括肿瘤相关巨噬细胞(TAMs)和髓源性抑制细胞(MDSCs),在促进肿瘤进展和抑制免疫活性方面发挥核心作用。MDSCs主要分为单核细胞型(M-MDSC)和粒细胞型(PMN-MDSC)亚群,在小鼠神经母细胞瘤模型和人类患者中均显著增加,并促进免疫抑制、损害T细胞和NK细胞功能。本综述总结了神经母细胞瘤中的髓系细胞格局,涵盖MDSCs的起源与发育、MDSC亚群的表型和功能多样性、驱动MDSC募集和免疫抑制活性的机制,以及增强免疫治疗疗效的新兴治疗策略,包括靶向MDSCs和调控铁死亡以重编程其功能的方法。
展开英文摘要原文
Neuroblastoma is the most common extracranial pediatric solid tumor. Although the incorporation of anti-GD2 immunotherapy into standard care has improved outcomes, five-year survival for high-risk patients remains below 50%. This highlights that, while immunotherapy holds promise in this pediatric cancer, neuroblastoma has developed multiple immunosuppressive mechanisms that limit anti-tumor immune responses. Among these, myeloid cells, including tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) play a central role in promoting tumor progression and suppressing immune activity. MDSCs, which are primarily classified into monocytic (M-MDSC) and granulocytic (PMN-MDSC) subsets, are markedly increased in both murine neuroblastoma models and human patients, where they promote immunosuppression and impair T cell and NK cell functions. This review summarizes the myeloid landscape in neuroblastoma, covering the origin and development of MDSCs, the phenotypic and functional diversity of MDSC subsets, the mechanisms driving MDSC recruitment and immunosuppressive activity, and emerging therapeutic strategies to enhance immunotherapy efficacy, including approaches to target MDSCs and modulate ferroptosis to reprogram their function.
论文信息
- 作者
- Choo HS、Yu T、Pham T、Singh N、Joshi S
- 单位
- Department of Pediatrics, Division of Pediatric Hematology-Oncology, Moores Cancer Center, University of California, San Diego, CA, United States.United States
- 文献类型
- 综述
- 期刊
- Frontiers in immunology2026