The immune microenvironment in gliomas, particularly those with oncohistone mutations such as H3.3K27M and G34R/V, has been a focal point of recent research. Andrade et al. conducted a comprehensive analysis of the immune tumor microenvironment (TME) using advanced transcriptomic, proteomic, and spatial single-cell techniques. Their findings revealed a complex landscape of myeloid populations that not only vary in composition but also exhibit tumor-promoting functions. This study highlights the critical role of the immune infiltrate in shaping the tumor's behavior and progression, suggesting that the immune TME is not merely a passive bystander but actively contributes to glioma pathology (ref: Andrade doi.org/10.1038/s41467-024-52096-w/). The research underscores the necessity of understanding the immune interactions within gliomas, as these insights could lead to novel therapeutic strategies targeting the immune system to improve patient outcomes. Furthermore, the study emphasizes the importance of utilizing diverse methodologies to capture the multifaceted nature of the immune landscape, which has been historically underexplored compared to the tumor cells themselves.