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.

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.

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