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

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.

Zinc phthalocyanine loaded- antibody functionalized nanoparticles enhance photodynamic therapy in monolayer (2-D) and multicellular tumour spheroid (3-D) cell cultures

“…However, these models consist of basic monolayers of cells grown on flat surfaces, and thus, they are incapable of authentically reproducing the intricate microenvironment found within cells or the numerous interactions that often occur between cellular and non-cellular components (Winifred Nompumelelo Simelane and Abrahamse, 2021;Kucinska et al, 2021). Moreover, in contrast to 3-D cell cultures, 2-D monolayer cell cultures lack the appropriate microenvironment and nutritional gradient often observed within solid tumours (Kucinska et al, 2021;Dalir Abdolahinia and Han, 2023). Therefore, some of the limitations often associated with using conventional 2-D monolayer cell cultures to investigate the photocytotoxicity effects of actively targeted PDT can be addressed by adopting 3-D cell cultures such as MCTSs (Winifred Nompumelelo Simelane and Abrahamse, 2021;Rossi and Blasi, 2022).…”

“…Studies have reported on the potential of actively targeted delivery of PS by specific ligands or moieties-functionalized nanoparticles on CRC cells cultured in two-dimensional (2D) systems ( Winifred Nompumelelo Simelane and Abrahamse, 2021 ). Nevertheless, recent findings have indicated several limitations associated with these culture models, such as alterations in cell shape, function, and responses, as well as the absence of interactions between cells and their surroundings ( Kucinska et al, 2021 ; Dalir Abdolahinia and Han, 2023 ). Consequently, this led to the use of 3-D in vitro cell models such as multicellular tumour spheroids (MCTSs) ( Mohammad-Hadi et al, 2018 ).…”

Application of Scaffold-Based Drug Delivery in Oral Cancer Treatment: A Novel Approach

“…This is particularly beneficial in oral cancer treatment, where tissue damage from surgery or radiation therapy can impede healing. By promoting tissue regeneration, scaffolds help restore the normal function of the affected area, aiding in the overall recovery process [ 80 , 85 , 86 ].…”

“…For instance, anti-cancer drug-coated scaffolds have demonstrated the ability to inhibit cancer cell proliferation effectively. This localized drug delivery approach not only targets the tumor more efficiently but also helps in mitigating the severity and extent of side effects commonly associated with conventional therapies [ 86 , 87 ].…”

“…Three-dimensional (3D) scaffolds play a central role in the treatment of oral cavity cancer. They allow for targeted or localized delivery of therapeutics, thereby reducing systemic side effects and improving therapeutic outcomes [ 51 , 85 , 86 ]. These scaffolds have been used extensively for the engineering of various oral tissues.…”