Recent advancements in 3D culture models have significantly enhanced our understanding of glioma biology, particularly in modeling the tumor microenvironment. One notable study developed a gelatin methacrylate hydrogel (3D-GMH) culture model that closely resembles the mesenchymal-like state of glioblastoma cells found in perivascular and hypoxic regions. This model not only captures the cellular phenotype characteristic of these niches but also facilitates the recruitment of macrophages through cytokine secretion, a hallmark of the mesenchymal phenotype (ref: Shah doi.org/10.1038/s41598-021-97059-z/). The findings indicate that 3D-GMH models provide a more accurate representation of glioma behavior compared to traditional neurosphere cultures, which predominantly enrich for cells from the infiltrative edge of the tumor. This distinction is crucial for understanding glioma progression and the tumor's interaction with the immune system. Moreover, the 3D-GMH model's ability to mimic the in situ conditions of glioblastoma allows researchers to investigate therapeutic responses and the tumor's microenvironmental influences more effectively. The study highlights the importance of using physiologically relevant models to explore glioma biology, as traditional 2D cultures often fail to replicate the complex interactions present in vivo. By employing 3D culture systems, researchers can better assess the efficacy of potential treatments and the role of immune cell interactions, paving the way for more targeted and effective therapeutic strategies in glioblastoma management.