Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Department of Immunology, Tianjin Medical University, Tianjin 300070, China; Department of Paediatrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Paediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Department of Immunology, Tianjin Medical University, Tianjin 300070, China.
Int Immunopharmacol. 2024 May 30;133:112145. doi: 10.1016/j.intimp.2024.112145. Epub 2024 Apr 30.
Treatment strategies for paediatric neuroblastoma as well as many other cancers are limited by the unfavourable tumour microenvironment (TME). In this study, the TMEs of neuroblastoma were grouped by their genetic signatures into four distinct subtypes: immune enriched, immune desert, non-proliferative and fibrotic. An Immune Score and a Proliferation Score were constructed based on the molecular features of the subtypes to quantify the immune microenvironment or malignancy degree of cancer cells in neuroblastoma, respectively. The Immune Score correlated with a patient's response to immunotherapy; the Proliferation Score was an independent prognostic biomarker for neuroblastoma and proved to be more accurate than the existing clinical predictors. This double scoring system was further validated and the conserved molecular pattern associated with immune landscape and malignancy degree was confirmed. Axitinib and BI-2536 were confirmed as candidate drugs for neuroblastoma by the double scoring system. Both in vivo and in vitro experiments demonstrated that axitinib-induced pyroptosis of neuroblastoma cells activated anti-tumour immunity and inhibited tumour growth; BI-2536 induced cell cycle arrest at the S phase in neuroblastoma cells. The comprehensive double scoring system of neuroblastoma may predict prognosis and screen for therapeutic strategies which could provide personalized treatments.
治疗小儿神经母细胞瘤和许多其他癌症的策略受到不利的肿瘤微环境（TME）的限制。在这项研究中，神经母细胞瘤的 TME 根据其遗传特征分为四个不同的亚型：免疫富集型、免疫荒漠型、非增殖型和纤维型。基于亚型的分子特征构建了免疫评分和增殖评分，分别定量神经母细胞瘤中癌细胞的免疫微环境或恶性程度。免疫评分与患者对免疫治疗的反应相关；增殖评分是神经母细胞瘤的独立预后生物标志物，比现有临床预测因子更准确。该双重评分系统进一步得到验证，并证实了与免疫景观和恶性程度相关的保守分子模式。双重评分系统证实阿昔替尼和 BI-2536 是神经母细胞瘤的候选药物。体内和体外实验均表明，阿昔替尼诱导神经母细胞瘤细胞的细胞焦亡激活了抗肿瘤免疫并抑制了肿瘤生长；BI-2536 诱导神经母细胞瘤细胞的细胞周期在 S 期停滞。神经母细胞瘤的综合双重评分系统可以预测预后并筛选治疗策略，为患者提供个性化治疗。
