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This review synthesizes GSC niche interactions, macrophage involvement, pyroptosis/ferroptosis-related theories, metabolic adaptations, strategies to convert cold to hot TME, and advances in GBM immunotherapy and models.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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10.3233/CBM-230486 IOS Press  \nGlioma stem cells remodel immunotolerant microenvironment in GBM and are associated with therapeutic advancements  \nXifeng Feia ; 1 , Jie Wub ; 1 , Haiyan Tianc ; 1 , Dongyi Jianga , Hanchun Chena , Ke Yanb , Yuan Wangd , Yaodong Zhaoe , Hua Chenf , Xiangtong Xiea , Zhimin Wanga ;g ;􀀃 , Wenyu Zhub ;􀀃 and Qiang Huangha Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, Jiangsu, China  \nb Department of Neurosurgery, The Affiliated Suzhou Science and Technology Town Hospital of Nanjing University Medical School, Suzhou, Jiangsu, China  \nc Department of GCP, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, Jiangsu, China  \nd Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China e Department of Neurosurgery, Shanghai General Hospital, Shanghai, China  \nf Department of Neurosurgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China g Department of Neurosurgery, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China h Department of Neurosurgery, Second Affiliated Hospital of Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China  \nReceived 15 November 2023 Accepted 19 July 2024  \nAbstract. Glioma is the most common primary tumor of the central nervous system (CNS) . Glioblastoma (GBM) is incurable with current treatment strategies. Additionally, the treatment of recurrent GBM (rGBM) is often referred to as terminal treatment, necessitating hospice-level care and management. The presence of the blood-brain barrier (BBB) gives GBM a more challenging or “cold” tumor microenvironment (TME) than that of other cancers and gloma stem cells (GSCs) play an important role in the TME remodeling, occurrence, development and recurrence of giloma. In this review, our primary focus will be on discussing the following topics: niche-associated GSCs and macrophages, new theories regarding GSC and TME involving pyroptosis and ferroptosis in GBM, metabolic adaptations of GSCs, the influence of the cold environment in GBM on immunotherapy, potential strategies to transform the cold GBM TME into a hot one, and the advancement of GBM immunotherapy and GBM models.  \nKeywords: Glioma stem cells, niche, glioma cold environment, immunotherapy, GBM models  \n1Xifeng Fei, Jie Wu and Haiyan Tian contribute equally to the article.  \n􀀃 Corresponding authors: Wenyu Zhu, Department of Neurosurgery, the Affiliated Suzhou Science and Technology Town Hospital of Nanjing University Medical School, Suzhou 215163, Jiangsu, China. E-mail: [zwy2000@sina.com. Zhimin Wang](zwy2000@sina.com. Zhimin Wang), Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou 215127, Jiangsu, China. E-mail: [wangzm2017@126.com](wangzm2017@126.com).  \n1. Introduction  \nGlioblastoma multiforme (GBM) is the most common intracranial malignant tumor, and its prognosis has not made significant progress, despite the advances in treatments. In the 2021 edition of the WHO classification, gliomas lacking IDH mutations that have concomitant +7/􀀀10 chromosome copy number changes, EGFR gene amplification, or TERT promoter mutations  \nISSN 1574-0153 􀀍c 2024 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4 .0) .  \n2 X. Fei et al. / Glioma stem cells and immunotolerant microenvironment  \nFig. 1. All tumors lacking IDH mutations with concomitant gain of chromosome 7 and loss of chromosome 10, EGFR amplification, or TERT promoter mutations are referred to as glioblastomas.  \nare called glioblastoma and are given a WHO grade of 4 [1](Fig. 1) . Glioma stem cells (GSCs) in GBMare a small group of cells with low proliferative activity and drug resistance that are associated w","cbCaic4oZFzZzLPj","https://ap.wps.com/l/cbCaic4oZFzZzLPj","pdf",984413,24,"English","# Abstract\n# Introduction\n# Glioma stem cells and immune-related niches\n## TME and glioma stem cells","[{\"question\":\"Why is GBM described as having a “cold” tumor microenvironment?\",\"answer\":\"The blood-brain barrier and associated features create a “cold” TME, making the environment more challenging for therapy and drug delivery compared with other cancers.\"},{\"question\":\"What role do glioma stem cells (GSCs) play in GBM progression?\",\"answer\":\"GSCs are linked to tumor recurrence and refractory behavior, and they remodel the host tissues, contributing to immunotolerant microenvironments.\"},{\"question\":\"Which approaches does the review discuss for improving GBM immunotherapy?\",\"answer\":\"It emphasizes strategies to convert the cold GBM TME into a hot one, including targeting pathways involving pyroptosis and ferroptosis, using single-cell sequencing to find regulatory molecules, and developing targeted therapies.\"}]","Glioma stem cells remodel immunotolerant microenvironment in GBM and are associated with therapeutic advancements | PDF",1789993238]