GSCs in the Transdifferentiation Phenomenon: Focus on CAR-T-Based Therapy

TL;DR

This paper reviews how glioblastoma stem cells change into other cell types and how CAR-T therapy could target them to improve treatment outcomes.

Contribution

The paper integrates current knowledge on GSC transdifferentiation with emerging CAR-T therapies to propose next-generation treatment strategies.

Findings

GSCs undergo transdifferentiation to promote tumor vascularization and immune suppression.

CAR-T therapies show potential to target and eliminate GSCs, overcoming treatment resistance.

Combining GSC biology with immunotherapy could improve glioblastoma outcomes.

Abstract

Glioblastoma (GBM) remains one of the most lethal brain tumors, largely due to the resilience and plasticity of glioblastoma stem cells (GSCs), which drive tumor growth, recurrence, and resistance to conventional therapies. A key mechanism underlying their aggressiveness is transdifferentiation, whereby GSCs acquire endothelial- and pericyte-like phenotypes, promoting neovascularization and remodeling the tumor microenvironment to sustain malignancy. Conventional treatments often fail to eliminate these resilient populations, highlighting the need for innovative targeted strategies. Chimeric antigen receptor (CAR)-based immunotherapies offer a targeted strategy to specifically eliminate GSCs and interfere with their role in promoting tumor vascularization and suppressing immune responses. This review aims to provide a comprehensive overview of the molecular mechanisms driving GSC transdifferentiation and to summarize the current landscape of CAR-T therapies developed to target these cells. By integrating knowledge of GSC biology with advances in CAR-T-based interventions, this work highlights the potential of next-generation immunotherapies to overcome therapeutic resistance, limit tumor recurrence, and improve clinical outcomes in GBM.

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