Strategies for the vascularization and immune modeling of human tumor organoids based on advanced technologies

Since tumors are highly dynamic and heterogeneous, tumor patients show great individual differences in their response to the same clinical anticancer therapy. Therefore, there is an urgent need for in vitro tumor models with patient-specific pathophysiological characteristics, which would provide a platform for both basic tumor transformation and clinical trials, thereby advancing personalized and precise treatment of tumors. Tumor organoids can be defined as three-dimensional ​(3D) cell clusters derived from tumor cells capable of replicating key features of primary tumor tissue, including their cellular heterogeneity, genetic mutations, and histological architecture. To date, tumor organoid models, including those of the brain, intestine, stomach, liver, kidney, lung and other tissue types, have been successfully constructed. In this review, we systematically summarize the vascularization and immune modeling of human tumor organoids in vitro , including scaffold materials and advanced technologies such as organ-on-a-chip, 3D bioprinting, genetic engineering and artificial intelligence (AI). The applications of tumor organoid models in basic research and personalized treatment are then introduced. Finally, the current challenges and future prospects of this field are emphasized, which is highly important for promoting progress and broadening the application of tumor organoids. • High tumor heterogeneity and tumor dynamics are closely related to treatment resistance, thereby leading to a poor prognosis. • Diverse tumor organoids have the ability to mimic various crucial characteristics of primary tumor tissues. • Advanced technologies applied in the construction of tumor organoids facilitates personalized and precise tumor therapies.