Related Experiment Video
Updated: Jan 27, 2026

A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery
Published on: February 28, 2020
3D-3 Tumor Models in Drug Discovery for Analysis of Immune Cell Infiltration
Annika Osswald1, Viola Hedrich1, Wolfgang Sommergruber2
1Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.
Abstract:
The cross talk between tumor cells and other cells present in the tumor microenvironment such as stromal and immune cells highly influences the behavior and progression of disease. Understanding the underlying mechanisms of interaction is a prerequisite to develop new treatment strategies and to prevent or at least reduce therapy failure in the future. Specific reactivation of the patient's immune system is one of the major goals today. However, standard two-dimensional (2D) cell culture techniques lack the necessary complexity to address related questions. Novel three-dimensional (3D) in vitro models-embedded in a matrix or encapsulated in alginate-recapitulate the in vivo situation much better. Cross talk between different cell types can be studied starting from co-cultures. As cancer immune modulation is becoming a major research topic, 3D in vitro models represent an important tool to address immune regulatory/modulatory questions for T, NK, and other cells of the immune system. The 3D systems consisting of tumor cells, fibroblasts, and immune cells (3D-3) already proved as a reliable tool for us. For instance, we made use of those models to study the molecular mechanisms of the cross talk of non-small cell lung cancer (NSCLC) and fibroblasts, to unveil macrophage plasticity in the tumor microenvironment and to mirror drug responses in vivo. Generation of those 3D models and how to use them to study immune cell infiltration and activation will be described in the present book chapter.
Insights
Three-dimensional (3D) in vitro models better mimic the tumor microenvironment than 2D cultures. These advanced models are crucial for studying cancer immune modulation and developing new therapies.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Tumor microenvironment interactions critically impact cancer progression and treatment outcomes.
- Standard 2D cell cultures inadequately represent in vivo complexity for studying cell-cell communication.
- Reactivating the patient's immune system is a key therapeutic goal.
Purpose of the Study:
- To highlight the utility of novel three-dimensional (3D) in vitro models for cancer research.
- To demonstrate how 3D models can elucidate tumor microenvironment interactions.
- To present 3D models as a tool for studying cancer immune modulation.
Main Methods:
- Development and utilization of advanced 3D in vitro models, including matrix-embedded or alginate-encapsulated systems.
- Co-culture of tumor cells, stromal cells (fibroblasts), and immune cells (T, NK, macrophages) in 3D systems (3D-3).
- Application of 3D models to investigate molecular crosstalk, macrophage plasticity, and drug responses.
Main Results:
- 3D in vitro models, such as 3D-3 systems, effectively recapitulate in vivo tumor microenvironment complexity.
- These models facilitate the study of molecular mechanisms underlying cancer cell-host cell interactions.
- 3D models have been successfully used to study non-small cell lung cancer (NSCLC) and fibroblast crosstalk, macrophage plasticity, and in vivo drug responses.
Conclusions:
- Novel 3D in vitro models offer a superior platform for studying complex tumor microenvironment dynamics compared to traditional 2D cultures.
- 3D models are essential for advancing research in cancer immune modulation, including immune cell infiltration and activation.
- The described 3D systems provide a reliable tool for investigating therapeutic strategies and reducing treatment failure.
Related Concept Videos
Drug Discovery: Overview
What is the Immune System?
Therapeutic Drug Monitoring: Drug Analysis Methods
Cell-mediated Immune Responses
Cells of the Adaptive Immune Response
Humoral Immune Responses

