2. Academic Validation
  3. Comprehensive quantifications of tumour microenvironment to predict the responsiveness to immunotherapy and prognosis for paediatric neuroblastomas

Comprehensive quantifications of tumour microenvironment to predict the responsiveness to immunotherapy and prognosis for paediatric neuroblastomas

  • Int Immunopharmacol. 2024 May 30:133:112145. doi: 10.1016/j.intimp.2024.112145.
Mingkun Song 1,  Yiming Sun 2,  Yikai Hu 2,  Chong Wang 3,  Yan Jin 4,  Yun Liu 4,  Yurong Da 5,  Qiang Zhao 6,  Rongxiu Zheng 7,  Long Li 8
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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; Class of 2019, Program in Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
  • 4 Department of Paediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
  • 5 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. Electronic address: dayr@tmu.edu.cn.
  • 6 Department of Paediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. Electronic address: zhaoqiang@tjmuch.com.
  • 7 Department of Paediatrics, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: rzheng@tmu.edu.cn.
  • 8 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 Paediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. Electronic address: Long.Li@tmu.edu.cn.
PMID: 38691920 DOI: 10.1016/j.intimp.2024.112145
Abstract

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.

Keywords

Axitinib; Immunotherapy; Neuroblastoma; Pyroptosis; Tumor microenvironment.

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