Abstract
Tumor organoids have emerged as powerful tools for in vitro cancer research due to their ability to retain the structural and genetic characteristics of tumors. Nevertheless, the absence of a complete tumor microenvironment (TME) limits the broader application of organoid models in immunological studies. Given the critical role of immune cells in tumor initiation and progression, the co-culture model of organoids and peripheral blood mononuclear cells (PBMCs) may provide an effective platform for simulating the interactions between immune and tumor cells in vitro. This model stands as a robust instrument for dissecting the TME, elucidating the molecular interactions, and exploring the therapeutic applications of chimeric antigen receptor (CAR)-engineered lymphocytes, as well as other cancer treatment modalities. This review systematically evaluates the advantages and disadvantages of the co-culture model, identifies its technical bottlenecks, and proposes corresponding optimization strategies. By summarizing the latest research advancements in this co-culture model, our goal is to provide valuable insights for further model optimization and clinical application, thereby promoting immunological research and bridging the gap between experimental outcomes and clinical practice.