Opportunities to Modulate Tumor Ecosystem Toward Successful Glioblastoma Immunotherapy

Over the past decade, the failure of multiple clinical trials has confirmed the need for a systematic and comprehensive understanding of glioblastoma (GBM). Current immunotherapies aiming to harness the immune system to achieve anti-tumor effects remain largely ineffective, highlighting the complexities of the GBM microenvironment. However, our recent understanding of immune niches within the central nervous system provides both opportunities and challenges in translating these insights into successful immunotherapy implementation. We discuss these strategies, including targeting multiple antigens within the heterogeneous GBM microenvironment, identifying new druggable targets to abrogate immunosuppression, and understanding niche-specific immune cell functionality to modulate tumor-immune-stroma interactions.