Research progress on the interaction between glioblastoma and its microenvironment

doi:10.16098/j.issn.0529-1356.2025.01.009

Abstract

Abstract:

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor of the central nervous system in adults, with a median survival of less than 15 months. The tumor microenvironment (TME) of GBM includes extracellular matrix and a variety of immune cells, including tumor-associated macrophages, microglia and myeloid-derived suppressor cells. The interaction between these cells and tumor cells plays a key role in the occurrence and development of GBM. The heterogeneity of GBM microenvironment is one of the main reasons for the poor efficacy of many therapies. Therefore, understanding the interaction between GBM and its tumor microenvironment is helpful to explore new targeted therapeutic strategies, which is expected to provide better treatment options for patients, thereby improving patient prognosis.

Key words: Glioblastoma, Tumor microenvironment, Heterogeneity, Tumor-associated macrophage

CLC Number:

R739.41

FU Hai-tao LIU xing LIU Yu-qing . Research progress on the interaction between glioblastoma and its microenvironment[J]. Acta Anatomica Sinica, 2025, 56(1): 66-73.

References

［1］Lapointe S，Perry A，Butowski NA. Primary brain tumours in adults［J］. Lancet, 2018, 392(10145): 432-446.

［2］Ostrom QT，Patil N，Cioffi G，et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013-2017［J］. Neuro Oncol, 2020, 22(12 Suppl 2):iv1-iv96.

［3］Stupp R，Mason WP，van den Bent MJ，et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma［J］. N Engl J Med, 2005, 352(10): 987-996.

［4］Yasinjan F，Xing Y，Geng H，et al. Immunotherapy: a promising approach for glioma treatment［J］. Front Immunol, 2023, 14: 1255611.

［5］Quail DF，Joyce JA. The microenvironmental landscape of brain tumors［J］. Cancer Cell,2017,31(3):326-341.

［6］Hoogstrate Y，Draaisma K，Ghisai SA，et al. Transcriptome analysis reveals tumor microenvironment changes in glioblastoma［J］. Cancer Cell,2023,41(4):678-692.e7.

［7］Engelhardt B，Vajkoczy P，Weller RO. The movers and shapers in immune privilege of the CNS［J］. Nat Immunol,2017,18(2):123-131.

［8］Belousov A，Titov S，Shved N，et al. The extracellular matrix and biocompatible materials in glioblastoma treatment［J］.Front Bioeng Biotechnol,2019,7:341.

［9］Wei R，Zhou J，Bui B，et al. Glioma actively orchestrate a self-advantageous extracellular matrix to promote recurrence and progression［J］. BMC Cancer,2024,24(1):974.

［10］Di Vito A，Donato A，Bria J，et al. Extracellular matrix structure and interaction with immune cells in adult astrocytic tumors［J］. Cell Mol Neurobiol,2024,44(1):54.

［11］Collado J，Boland L，Ahrendsen JT，et al. Understanding the glioblastoma tumor microenvironment: leveraging the extracellular matrix to increase immunotherapy efficacy［J］.Front Immunol,2024,15:1336476.

［12］Pietrobono D，Giacomelli C，Marchetti L，et al. High adenosine extracellular levels induce glioblastoma aggressive traits modulating the mesenchymal stromal cell secretome［J］.Int J Mol Sci, 2020,21(20):7706.

［13］Sun R，Kim AH. The multifaceted mechanisms of malignant glioblastoma progression and clinical implications［J］. Cancer Metastasis Rev,2022,41(4):871-898.

［14］Xuan W，Lesniak MS，James CD，et al. Context-dependent glioblastoma-macrophage/microglia symbiosis and associated mechanisms［J］. Trends Immunol,2021,42(4):280-292.

［15］Cheng N，Bai X，Shu Y，et al. Targeting tumor-associated macrophages as an antitumor strategy［J］.Biochem Pharmacol,2021,183:114354.

［16］Yekula A，Yekula A，Muralidharan K，et al. Extracellular vesicles in glioblastoma tumor microenvironment［J］.Front Immunol,2020,10:3137.

［17］Dumas AA，Pomella N，Rosser G，et al. Microglia promote glioblastoma via mTOR-mediated immunosuppression of the tumour microenvironment［J］.Embo J,2020,39(15):e103790.

［18］Hutter G，Theruvath J，Graef CM，et al. Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma［J］. Proc Natl Acad Sci USA,2019,116(3):997-1006.

［19］Wu B，Zhan X，Jiang M. CD58 defines regulatory macrophages within the tumor microenvironment［J］. Commun Biol,2024,7(1):1025.

［20］Takenaka MC，Gabriely G，Rothhammer V，et al. Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39［J］.Nat Neurosci,2019,22(5):729-740.

［21］An W，Ren C，Yuan L，et al. High expression of SIGLEC7 may promote M2-type macrophage polarization leading to adverse prognosis in glioma patients［J］. Front Immunol,2024,15:1411072.

［22］Rivera-Ramos A，Cruz-Hernández L，Talaverón R，et al. Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth［J］.Cancer Letters,2024,591:216879.

［23］Chen Z，Wang J，Peng P，et al. Hypoxia-induced TGFBI maintains glioma stem cells by stabilizing EphA2［J］.Theranostics,2024,14(15):5778-5792.

［24］Mohme M，Schliffke S，Maire CL，et al. Immunophenotyping of newly diagnosed and recurrent glioblastoma defines distinct immune exhaustion profiles in peripheral and tumor-infiltrating lymphocytes［J］.Clin Cancer Res,2018,24(17):4187-4200.

［25］Dapash M，Hou D，Castro B，et al. The interplay between glioblastoma and its microenvironment［J］.Cells,2021,10(9):2257.

［26］Wing JB，Tanaka A，Sakaguchi S. Human FOXP3(+) regulatory T cell heterogeneity and function in autoimmunity and cancer［J］. Immunity,2019,50(2):302-316.

［27］Zhang S，Rao G，Heimberger A，et al. Fibrinogen-like protein 2: its biological function across cell types and the potential to serve as an immunotherapy target for brain tumors［J］.Cytokine Growth Factor Rev,2023,69:73-79.

［28］Li C，Jiang P，Wei S，et al. Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects［J］.Mol Cancer,2020,19(1):116.

［29］Hato L，Vizcay A，Eguren I，et al. Dendritic cells in cancer immunology and immunotherapy［J］.Cancers (Basel),2024,16(5):981.

［30］Zhou C，Ma L，Xu H，et al. Meningeal lymphatics regulate radiotherapy efficacy through modulating anti-tumor immunity［J］.Cell Res,2022,32(6):543-554.

［31］Friedmann-Morvinski D，Hambardzumyan D. Monocyte-neutrophil entanglement in glioblastoma［J］.J Clin Invest,2023,133(1):e163451.

［32］Wen J，Liu D，Zhu H，et al. Microenvironmental regulation of tumor-associated neutrophils in malignant glioma: from mechanism to therapy［J］. J Neuroinflammation,2024,21(1):226.

［33］Sun C，Wang S，Ma Z，et al. Neutrophils in glioma microenvironment: from immune function to immunotherapy［J］.Front Immunol,2024,15:1393173.

［34］Salemizadeh Parizi M，Salemizadeh Parizi F，Abdolhosseini S，et al. Myeloid-derived suppressor cells (MDSCs) in brain cancer: challenges and therapeutic strategies［J］. Inflammopharmacology,2021,29(6):1613-1624.

［35］Lin H，Liu C，Hu A，et al. Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives［J］. J Hematol Oncol,2024,17(1):31.

［36］Tian Y，Gao X，Yang X，et al. VEGFA contributes to tumor property of glioblastoma cells by promoting differentiation of myeloid-derived suppressor cells［J］.BMC Cancer,2024,24(1):1040.

［37］Pant A，Hwa-Lin Bergsneider B，Srivastava S，et al. CCR2 and CCR5 co-inhibition modulates immunosuppressive myeloid milieu in glioma and synergizes with anti-PD-1 therapy［J］.OncoImmunology,2024,13(1):2338965.

［38］Elguindy M，Young JS，Mondal I，et al. Glioma-immune cell crosstalk in tumor progression［J］.Cancers (Basel),2024,16(2):308.

［39］Singh MK，Bhattacharya D，Chaudhuri S，et al. T11TS inhibits glioma angiogenesis by modulation of MMPs,TIMPs,with related integrin αv and TGF-β1 expressions［J］.Tumour Biol,2014,35(3):2231-2246.

［40］Ye XZ，Xu SL，Xin YH，et al. Tumor-associated microglia/macrophages enhance the invasion of glioma stem-like cells via TGF-β1 signaling pathway［J］.J Immunol,2012,189(1):444-453.

［41］Rosberg R，Smolag KI，Sjolund J，et al. Hypoxia-induced complement component 3 promotes aggressive tumor growth in the glioblastoma microenvironment［J］.JCI Insight,2024,9(19):e179854.

［42］Mi Y，Guo N，Luan J，et al.The emerging role of myeloid-derived suppressor cells in the glioma immune suppressive microenvironment［J］.Front Immunol,2020,11:737.

［43］Groth C，Hu X，Weber R，et al. Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression［J］.Br J Cancer,2019,120(1):16-25.

［44］Prager BC，Bhargava S，Mahadev V，et al. Glioblastoma stem cells: driving resilience through chaos［J］.Trends Cancer,2020,6(3):223-235.

［45］Biserova K，Jakovlevs A，Uljanovs R，et al. Cancer stem cells: significance in origin, pathogenesis and treatment of glioblastoma［J］.Cells,2021,10(3):621.

［46］Wang H，Yao L，Chen J，et al. The dual role of POSTN in maintaining glioblastoma stem cells and the immunosuppressive phenotype of microglia in glioblastoma［J］. J Exp Clin Cancer Res,2024,43(1):252.

［47］Yu T，Wang K，Wang J，et al. M-MDSCs mediated trans-BBB drug delivery for suppression of glioblastoma recurrence post-standard treatment［J］. J Control Release,2024,369:199-214.

［48］Rodriguez SMB，Tataranu LG，Kamel A，et al. Glioblastoma and immune checkpoint inhibitors: a glance at available treatment options and future directions［J］. Int J Mol Sci,2024,25(19):10765.

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