The tumor microenvironment (TME) plays a crucial role in the progression and treatment resistance of glioblastoma (GBM). Recent studies have highlighted the importance of tumor-associated macrophages (TAMs) in mediating immune responses and influencing the efficacy of immunotherapies such as anti-PD-1 therapy. For instance, Zhao et al. demonstrated that blocking integrin alpha 5 (ITGA5) can enhance the effectiveness of anti-PD-1 therapy by remodeling TAMs, which are often immunosuppressive and contribute to the resistance against such treatments (ref: Zhao doi.org/10.1002/cac2.70016/). This finding underscores the need to understand the cellular heterogeneity within the TME to develop more effective immunotherapeutic strategies. Furthermore, Bejarano et al. provided a comprehensive single-cell atlas of endothelial and mural cells across various brain tumors, including primary gliomas and brain metastases, revealing significant alterations in the blood-brain barrier (BBB) architecture that could impact therapeutic delivery and immune cell infiltration (ref: Bejarano doi.org/10.1016/j.immuni.2025.02.022/). Their analysis indicates that the TME is not only a passive environment but actively participates in tumor progression and response to therapy, emphasizing the complexity of immune interactions in GBM.