The tumor microenvironment (TME) in glioblastoma is characterized by a complex interplay between tumor cells and immune components, particularly macrophages and microglia. A study identified a subset of monocyte-derived tumor-associated macrophages (Mo-TAMs) that are localized to the peri-necrotic niche, exhibiting a hypoxia response signature that may contribute to tumor progression and therapeutic resistance (ref: Wang doi.org/10.1016/j.ccell.2024.03.013/). This finding highlights the heterogeneity of Mo-TAMs and their potential role in vasculature normalization, suggesting that targeting these cells could enhance treatment efficacy. Additionally, research demonstrated that glioblastoma-instructed microglia transition to various phenotypic states, exhibiting both phagocytic and dendritic cell-like features, which are crucial for supporting tumor growth and modulating immune responses (ref: Yabo doi.org/10.1186/s13073-024-01321-8/). The study emphasizes the importance of understanding microglial plasticity in the context of therapeutic interventions, particularly in response to temozolomide treatment, which alters the crosstalk between tumor cells and TME components. Furthermore, spatial transcriptomics revealed significant immunosuppression within the necrotic and perinecrotic niches, underscoring the need for strategies that can effectively target these immunosuppressive environments to improve patient outcomes (ref: Liu doi.org/10.1186/s40478-024-01769-0/).