While immunotherapies have revolutionized treatment for other cancers, glioblastoma multiforme (GBM) patients have not shown similar positive responses. The limited response to immunotherapies is partly due to the unique challenges associated with the GBM tumor microenvironment (TME), which promotes resistance to immunotherapies, causing many promising therapies to fail. There is, therefore, an urgent need to develop strategies that make the TME immune permissive to promote treatment efficacy. Bioactive nano-delivery systems, in which the nanoparticle, due to its chemical composition, provides the pharmacological function, have recently emerged as an encouraging option for enhancing the efficacy of immunotherapeutics. These systems are designed to overcome immunosuppressive mechanisms in the TME to improve the efficacy of a therapy. This review will discuss different aspects of the TME and how they impede therapy success. Then, we will summarize recent developments in TME-modifying nanotherapeutics and the in vitro models utilized to facilitate these advances.
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