Endothelial cells sense temozolomide resistance to facilitate monocyte-derived macrophage infiltration in glioblastoma
This study identifies a novel signaling cascade whereby TMZ-resistant GBM secretes COL6A1 to activate an IKZF1-UBD axis in ECs, disrupting blood vessel integrity and facilitating MDM infiltration. Our findings delineate the pivotal mechanism by which tumor cells engage ECs to drive MDM infiltration - a linchpin part of the positive-feedback loop that couples TMZ resistance to MDM influx. Targeting IKZF1 with LEN represents a promising strategy for restoring endothelial barrier function, reducing MDM infiltration, and enhancing chemosensitivity in GBM.
Authors
- Xiaoling She
- Xinmiao Long (ORCID: https://orcid.org/0000-0003-2898-0947)
- Minghua Wu (ORCID: https://orcid.org/0000-0001-5547-907X)
- Kun Deng
- Wei Gao (ORCID: https://orcid.org/0000-0003-1026-3878)
- Xuetong Li (ORCID: https://orcid.org/0000-0003-0029-2296)
- Qing Liu (ORCID: https://orcid.org/0009-0008-7432-9729)
- Jianliang Huang (ORCID: https://orcid.org/0000-0002-4700-0329)
- Meng Huang (ORCID: https://orcid.org/0000-0003-2575-9403)
- Xiangyu Wang (ORCID: https://orcid.org/0000-0001-9151-002X)
- Xiang Lin
Institutions
- Central South University (CN)
- Hunan Cancer Hospital (CN)
- Xiangya Hospital Central South University (CN)
Publication Details
- Journal
- Drug Resistance Updates
- Published
- 2025-11-22
- DOI
- https://doi.org/10.1016/j.drup.2025.101329
- Citations
- 3
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 4.88