3D models in the new era of immune oncology: focus on T cells, CAF and ECM

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, improving survival rates for many patients.
• However, intrinsic or acquired resistance to ICIs is a significant clinical challenge, necessitating better patient selection strategies.
• Understanding the tumor microenvironment (TME) is crucial for overcoming resistance and developing novel immunotherapies.

Purpose of the Study:

• To review current knowledge on the tumor microenvironment (TME) and its role in ICI resistance.
• To highlight key cellular and extracellular components of the TME, including T cells, cancer-associated fibroblasts (CAFs), and the extracellular matrix (ECM).
• To discuss the potential of 3D cell culture models for studying the TME and screening immunomodulatory drugs.

Main Methods:

• Literature review of current research on tumor microenvironment and immunotherapy.
• Focus on T cells, cancer-associated fibroblasts, and extracellular matrix interactions.
• Exploration of 3D cell culture models for TME research and drug screening.

Main Results:

• The TME, comprising diverse cell types and ECM components, significantly influences ICI efficacy.
• T cells, CAFs, and ECM dynamics are critical factors in both ICI sensitivity and resistance.
• 3D cell culture models offer a promising platform to recapitulate TME complexity and evaluate novel therapeutic strategies.

Conclusions:

• A deeper understanding of TME complexity is essential for advancing cancer immunotherapy.
• Targeting specific TME components and utilizing advanced models like 3D cultures can lead to more effective combined immunotherapeutic strategies.
• Biomarkers predictive of ICI response are needed for optimal patient selection and treatment planning.