MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmunotherapy and Microenvironment in Malignant Central Nervous System TumorsView all articles
Shaping the Glioblastoma Microenvironment to Enhance CAR-NK Immunotherapy
Provisionally accepted
- 1North Carolina School of Science and Mathematics, Durham, United States
- 2The University of Alabama at Birmingham Department of Biomedical Informatics and Data Science, Birmingham, United States
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Chimeric antigen receptor–natural killer (CAR-NK) cell therapy has shown favorable results in treating hematological malignancies but with limited efficacy against solid tumors, including glioblastomas, which is partly due to the immunosuppressive microenvironment of solid tumors. This mini review focuses on the various immunosuppressive strategies employed by the glioblastoma microenvironment for immune evasion, including stromal barriers, hypoxic conditions, immunosuppressive cytokines, downregulation of activating ligands, and upregulation of immune checkpoints. A range of emerging strategies has been proposed to counteract these inhibitory effects, such as genetic engineering of NK cells and molecular targeting of the stroma in combination with oncolytic virus therapy. Future single-cell spatiotemporal omics studies are expected to further enable a personalized and dynamic approach to treating glioblastoma with improved outcomes.
Keywords: glioblastomas, microenvironment, Chimeric Antigen Receptor, Natural Killer cell, Immunotherapy
Received: 08 Aug 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Tang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Emily Tang, emily.tang0324@gmail.com
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