3D Tumor Spheroid and Organoid to Model Tumor Microenvironment for Cancer Immunotherapy

The intricate microenvironment in which malignant cells reside is essential for the progression of tumor growth. Both the physical and biochemical features of the tumor microenvironment (TME) play a critical role in promoting the differentiation, proliferation, invasion, and metastasis of cancer cells. It is therefore essential to understand how malignant cells interact and communicate with an assortment of supportive tumor-associated cells including macrophages, fibroblasts, endothelial cells, and other immune cells. To study the complex mechanisms behind cancer progression, 3D spheroid and organoid models are widely in favor because they replicate the stromal environment and multicellular structure present within an in vivo tumor. It provides more precise data about the cell–cell interactions, tumor characteristics, drug discovery, and metabolic profile of cancer cells compared to oversimplified 2D systems and unrepresentative animal models. This review provides a description of the key elements of the tumor microenvironment as well as early research using cell-line derived, 3D spheroid tumor models that paved the way for the adoption of patient-derived spheroid and organoid models. In particular, 3D spheroid and organoid models provide a method for drug screening with a particular emphasis on influence of the TME in cancer immunotherapy.