The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment

Simple Summary The extensive array of applications in 3D culture models closely mimics the precise physiological conditions of in vivo settings, enabling the investigation of anticancer drug resistance, which suggests that, in addition to genes, cell structure significantly impacts toxicity outcomes. Commercial 3D culture systems offer a valuable platform to explore various facets of oral cancer research. These models present an ethical and reproducible alternative to animal studies, facilitating the examination of oral microbial population dynamics, cellular interactions between cancer cells and immune cells, and the role of macrophage cells in oral cancer.Abstract The onset and progression of oral cancer are accompanied by a dynamic interaction with the host immune system, and the immune cells within the tumor microenvironment play a pivotal role in the development of the tumor. By exploring the cellular immunity of oral cancer, we can gain insight into the contribution of both tumor cells and immune cells to tumorigenesis. This understanding is crucial for developing effective immunotherapeutic strategies to combat oral cancer. Studies of cancer immunology present unique challenges in terms of modeling due to the extraordinary complexity of the immune system. With its multitude of cellular components, each with distinct subtypes and various activation states, the immune system interacts with cancer cells and other components of the tumor, ultimately shaping the course of the disease. Conventional two-dimensional (2D) culture methods fall short of capturing these intricate cellular interactions. Mouse models enable us to learn about tumor biology in complicated and dynamic physiological systems but have limitations as the murine immune system differs significantly from that of humans. In light of these challenges, three-dimensional (3D) culture systems offer an alternative approach to studying cancer immunology and filling the existing gaps in available models. These 3D culture models provide a means to investigate complex cellular interactions that are difficult to replicate in 2D cultures. The direct study of the interaction between immune cells and cancer cells of human origin offers a more relevant and representative platform compared to mouse models, enabling advancements in our understanding of cancer immunology. This review explores commonly used 3D culture models and highlights their significant contributions to expanding our knowledge of cancer immunology. By harnessing the power of 3D culture systems, we can unlock new insights that pave the way for improved strategies in the battle against oral cancer.