Tumor Microenvironment and Metastasis Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin Pediatr. 2022 Feb 1;34(1):53-60. doi: 10.1097/MOP.0000000000001082.
The prognosis of pediatric patients with metastatic solid tumors remains poor, necessitating development of novel therapeutic strategies. The biology of the pediatric tumor microenvironment (TME) presents obstacles for the efficacy of current therapeutic approaches including immunotherapies. Targeting various aspects of the TME in pediatric patients with solid tumors represents a therapeutic opportunity that may improve outcomes. Here we will discuss recent advances in characterization of the TME, and clinical advances in targeting the immune, vascular, and stromal aspects of the TME.
Although immunotherapies have shown limited success in the treatment of pediatric solid tumor patients thus far, optimization of these approaches to overcome the TME shows promise. In addition, there is increasing focus on the myeloid compartment as a therapeutic target. Vascular endothelial growth factor (VEGF) targeting has resulted in responses in some refractory pediatric solid tumors. There has been relatively little focus on stromal targeting; however, emerging preclinical data are improving our understanding of underlying biology, paving the way for future therapies.
Although translation of TME-targeting therapies for pediatric solid tumors is in the early stages, we are optimistic that continued exploration of approaches aimed at rebalancing the TME will lead to improved outcomes for this population.
目的综述：转移性实体瘤患儿的预后仍然较差，需要开发新的治疗策略。儿科肿瘤微环境（TME）的生物学特性对当前治疗方法（包括免疫疗法）的疗效构成了障碍。针对实体瘤患儿 TME 的各个方面是一个治疗机会，可能会改善预后。本文将讨论 TME 的特征描述方面的最新进展，以及针对 TME 的免疫、血管和基质方面的临床进展。
最近的发现：尽管免疫疗法在治疗儿科实体瘤患者方面迄今为止取得了有限的成功，但优化这些方法以克服 TME 显示出了希望。此外，人们越来越关注髓系细胞作为治疗靶点。血管内皮生长因子（VEGF）靶向治疗已导致一些难治性儿科实体瘤有反应。对基质靶向的关注相对较少；然而，新出现的临床前数据正在提高我们对潜在生物学的理解，为未来的治疗铺平道路。
总结：尽管针对儿科实体瘤的 TME 靶向治疗的转化仍处于早期阶段，但我们乐观地认为，继续探索旨在重新平衡 TME 的方法将为该人群带来更好的结果。
