Hydrogel-Based Tumor Tissue Microarchitecture Reshapes Dendritic Cell Metabolic Profile and Functions

Area of Science:

• Immunology
• Biomaterials Science
• Cell Biology

Background:

• The extracellular matrix (ECM) is crucial for immune cell function and its remodeling is implicated in diseases like cancer.
• Fibrillar alignment within the ECM is a key feature of pathological conditions, influencing immune responses.

Purpose of the Study:

• To investigate the impact of extracellular matrix (ECM) alignment on dendritic cell (DC) behavior and function.
• To understand how controlled ECM anisotropy affects DC immunomodulatory properties and T-cell interactions.

Main Methods:

• Utilized 3D biomimetic collagen matrices with controlled fibril anisotropy to mimic ECM alignment.
• Analyzed immature and mature DC responses, including surface marker expression, chemokine secretion, transcriptomics, and metabolomics.
• Performed T-cell coculture experiments to assess the effect of ECM alignment on T-cell activation.

Main Results:

• Immature DCs in aligned matrices showed enhanced CD86 and HLA-DR expression and increased chemokine secretion but reduced oxidative phosphorylation and ATP production, leading to impaired migration.
• Mature DCs exhibited minimal sensitivity to ECM alignment, maintaining consistent functional profiles.
• ECM alignment dampened T-cell activation and proliferation in coculture experiments.

Conclusions:

• Extracellular matrix alignment differentially affects dendritic cell (DC) function based on their maturation state.
• ECM alignment can impair DC migration and T-cell responses, highlighting its role in immunomodulation within pathological contexts.
• These findings offer insights for developing therapies targeting cancer and inflammatory diseases by modulating the tumor microenvironment.