Overcoming immunotherapy resistance in glioblastoma: challenges and emerging strategies DOI Creative Commons
Mengmeng Fu, Bing Xue, Xiangshui Miao

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 28, 2025

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, characterized by rapid proliferation, extensive infiltration, significant intratumoral heterogeneity. Despite advancements conventional treatments, including surgery, radiotherapy, chemotherapy, prognosis for GBM patients remains poor, with a median survival of approximately 15 months. Immunotherapy has emerged as promising alternative; however, unique biological immunological features, its immunosuppressive microenvironment (TME) low mutational burden, render it resistant to many immunotherapeutic strategies. This review explores key challenges immunotherapy, focusing on immune evasion mechanisms, blood-brain barrier (BBB), TME. Immune checkpoint inhibitors CAR-T cells have shown promise preclinical models but limited clinical success due antigen heterogeneity, cell exhaustion, impaired trafficking across BBB. Emerging strategies, dual-targeting cells, engineered secreting therapeutic molecules, advanced delivery systems overcome BBB, show potential enhancing treatment efficacy. Addressing these crucial improving immunotherapy outcomes.

Язык: Английский

Overcoming immunotherapy resistance in glioblastoma: challenges and emerging strategies DOI Creative Commons
Mengmeng Fu, Bing Xue, Xiangshui Miao

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 28, 2025

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, characterized by rapid proliferation, extensive infiltration, significant intratumoral heterogeneity. Despite advancements conventional treatments, including surgery, radiotherapy, chemotherapy, prognosis for GBM patients remains poor, with a median survival of approximately 15 months. Immunotherapy has emerged as promising alternative; however, unique biological immunological features, its immunosuppressive microenvironment (TME) low mutational burden, render it resistant to many immunotherapeutic strategies. This review explores key challenges immunotherapy, focusing on immune evasion mechanisms, blood-brain barrier (BBB), TME. Immune checkpoint inhibitors CAR-T cells have shown promise preclinical models but limited clinical success due antigen heterogeneity, cell exhaustion, impaired trafficking across BBB. Emerging strategies, dual-targeting cells, engineered secreting therapeutic molecules, advanced delivery systems overcome BBB, show potential enhancing treatment efficacy. Addressing these crucial improving immunotherapy outcomes.

Язык: Английский

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