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

Sep 24, 2026

Uploaded by Rizky

Oral cancer onset and progression involve dynamic interactions with the host immune system, where immune cells in the tumor microenvironment are central to tumor development. Exploring cellular immunity reveals how tumor and immune components contribute to tumorigenesis and guides immunotherapeutic strategy design. Because immune modeling is uniquely challenging, conventional 2D culture inadequately captures complex cellular crosstalk, while mouse models are limited by major species immune differences. Three-dimensional culture systems address these gaps by enabling human-relevant, reproducible study of immune–cancer interactions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages28

Reading Time1 h 11 min

AccessFree to download

Introduction

Immune microenvironment in oral cancer

Limitations of 2D and mouse models

3D culture models and applications

Ethical and reproducible alternatives

Future perspectives

cancers Review The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment Elaheh Dalir Abdolahinia Citation: Dalir Abdolahinia, E.; Han, X. The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment. Cancers 2023, 15, 4266. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers15174266 Academic Editor: Yu-Chao Chang Received: 9 August 2023 Revised: 22 August 2023 Accepted: 22 August 2023 Published: 25 August 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . and Xiaozhe Han * Department of Oral Science and Translation Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA * Correspondence: [xhan@nova.edu](xhan@nova.edu); Tel.: +1-617-838-2188 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 asthe 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. Keywords: oral cancer; extracellular matrix; two/three-dimensional (2D/3D) model; immune cells; tumor cells; stromal cell 1. Introduction Head and neck cancers (HNCs), posit

FAQs

Why is the immune microenvironment important in oral cancer research?

Immune cells within the tumor microenvironment play a pivotal role in oral cancer development, and studying this interaction helps clarify contributions of both tumor and immune cells to tumorigenesis.

What limitations do conventional 2D culture methods have for studying oral cancer immunology?

2D cultures fall short of capturing the intricate cellular interactions required to model the complexity of the immune system and its influence on cancer progression.

How do 3D culture systems improve upon mouse models and 2D cultures?

3D systems provide a more relevant, human-origin platform to study immune–cancer interactions and address gaps left by 2D cultures, while avoiding key limitations of murine immune differences compared with humans.

Sep 24, 2026

Uploaded by Rizky