Frosch Jennifer, Leontari Ilia, Anderson John
UCL Institute of Child Health, Developmental Biology and Cancer Section, University College London, London WC1N 1EH, UK.
Cancers (Basel). 2021 Apr 6;13(7):1743. doi: 10.3390/cancers13071743.
Despite multimodal treatment, survival chances for high-risk neuroblastoma patients remain poor. Immunotherapeutic approaches focusing on the activation and/or modification of host immunity for eliminating tumor cells, such as chimeric antigen receptor (CAR) T cells, are currently in development, however clinical trials have failed to reproduce the preclinical results. The tumor microenvironment is emerging as a major contributor to immune suppression and tumor evasion in solid cancers and thus has to be overcome for therapies relying on a functional immune response. Among the cellular components of the neuroblastoma tumor microenvironment, suppressive myeloid cells have been described as key players in inhibition of antitumor immune responses and have been shown to positively correlate with more aggressive disease, resistance to treatments, and overall poor prognosis. This review article summarizes how neuroblastoma-driven inflammation induces suppressive myeloid cells in the tumor microenvironment and how they in turn sustain the tumor niche through suppressor functions, such as nutrient depletion and generation of oxidative stress. Numerous preclinical studies have suggested a range of drug and cellular therapy approaches to overcome myeloid-derived suppression in neuroblastoma that warrant evaluation in future clinical studies.
尽管采用了多模式治疗，但高危神经母细胞瘤患者的生存机会仍然很低。目前正在开发免疫治疗方法，如嵌合抗原受体（CAR）T细胞，其重点是激活和/或修饰宿主免疫以消除肿瘤细胞，然而临床试验未能重现临床前的结果。肿瘤微环境正在成为实体癌免疫抑制和肿瘤逃逸的主要因素，因此依赖功能性免疫反应的疗法必须克服这一因素。在神经母细胞瘤肿瘤微环境的细胞成分中，抑制性髓系细胞被认为是抑制抗肿瘤免疫反应的关键因素，并已被证明与更具侵袭性的疾病、对治疗的抗性以及总体不良预后呈正相关。这篇综述文章总结了神经母细胞瘤驱动的炎症如何在肿瘤微环境中诱导抑制性髓系细胞，以及它们如何通过营养物质消耗和氧化应激产生等抑制功能反过来维持肿瘤生态位。许多临床前研究提出了一系列药物和细胞治疗方法来克服神经母细胞瘤中髓系来源的抑制作用，值得在未来的临床研究中进行评估。
