Mechano-mediated M2 macrophage polarization and immune suppression in stiffened tumor microenvironment DOI Open Access
Jiranuwat Sapudom, Paul Sean Tipay, Jeremy Teo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 29, 2024

Abstract The tumor microenvironment (TME), which is composed of various cell types and the extracellular matrix (ECM), plays crucial roles in cancer progression treatment outcomes. However, impact mechanical properties ECM, specifically collagen fibril alignment crosslinking, on macrophage behavior polarization less understood. To investigate this, we reconstituted 3D matrices to mimic physical characteristics TME. Our results demonstrated that stiffening through or crosslinking fibrils promotes toward anti-inflammatory M2 phenotype. This phenotype characterized by increased expression CD105 CD206 a distinct cytokine secretion profile. stiffness aligned activate mechanotransduction pathways, notably integrin β1 PI3K signaling, leading IL-4 secretion, acts an autocrine manner further promote polarization. Interestingly, these stiffened microenvironments also suppressed proinflammatory response. In coculture experiments with breast lines (MDA-MB-231 MCF-7), macrophages within significantly proliferation invasion. These findings suggest its create more favorable environment for modulating activity. Overall, our study underscores critical role ECM mechanics shaping immune TME, highlighting potential therapies target inhibit enhance efficacy.

Language: Английский

Hydrogel‐Based Tumor Tissue Microarchitecture Reshapes Dendritic Cell Metabolic Profile and Functions DOI Open Access
Brian Chesney Quartey, Jiranuwat Sapudom, Paul Sean Tipay

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

The extracellular matrix (ECM) plays a pivotal role in immunomodulation, providing structural and biochemical cues that shape immune cell function. In pathological conditions like cancer chronic inflammation, dysregulated remodeling often results altered ECM composition architecture, with fibrillar alignment being hallmark linked to disease progression. Here, how influences dendritic (DC) behavior using 3D biomimetic collagen matrices controlled fibril anisotropy is investigated. This show immature DCs aligned exhibited increased expression of CD86 HLA-DR elevated secretion CXCL8 CCL2 chemokines, which may enhance recruitment. However, transcriptomic metabolomic analysis revealed significant downregulation oxidative phosphorylation an insufficient compensatory shift toward glycolysis, resulting reduced ATP production. metabolic constraint correlated impaired/reduced DC migratory speed distance. contrast, mature displayed minimal sensitivity alignment, maintaining uniform differentiation functional profiles across conditions. T-cell coculture experiments dampens activation proliferation, likely through direct modulation behavior. These findings highlight the stage-specific effects on function, highlighting its implications for therapeutic development other contexts.

Language: Английский

Citations

0
Application of Nanomaterials in the Repair and Regeneration of Lymphatic Organs and Corresponding Biophysical Simulation Strategies DOI Creative Commons
Bangheng Liu, Dong‐An Wang

Advanced NanoBiomed Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 9, 2024

Immune system diseases, malignant tumors, and traumatic injuries can directly damage the structure function of lymphoid organs, while subsequent radiotherapy, chemotherapy, lymph node dissection further patient's immune system, leading to dysfunction, metabolic disorders, increased susceptibility infection, which seriously affect prognosis quality life. In this context, nanotechnology plays a key role in organ regeneration recovery, including improving therapeutic effect through targeted drug delivery systems, using imaging probes achieve tumor prediction early detection, combining nanoplatforms with immunotherapy photodynamic therapy synergistic effects, nanomaterials regulate microenvironment enhance sensitivity traditional treatments. addition, biophysical simulation strategies that simulate organs have also attracted widespread attention, aiming construct native cell environment support functional recovery damaged tissues, or cells lymphocytes induce specific responses. The multifaceted application provides promising prospects for repair.

Language: Английский

Citations

1
Mechano-mediated M2 macrophage polarization and immune suppression in stiffened tumor microenvironment DOI Open Access
Jiranuwat Sapudom, Paul Sean Tipay, Jeremy Teo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 29, 2024

Abstract The tumor microenvironment (TME), which is composed of various cell types and the extracellular matrix (ECM), plays crucial roles in cancer progression treatment outcomes. However, impact mechanical properties ECM, specifically collagen fibril alignment crosslinking, on macrophage behavior polarization less understood. To investigate this, we reconstituted 3D matrices to mimic physical characteristics TME. Our results demonstrated that stiffening through or crosslinking fibrils promotes toward anti-inflammatory M2 phenotype. This phenotype characterized by increased expression CD105 CD206 a distinct cytokine secretion profile. stiffness aligned activate mechanotransduction pathways, notably integrin β1 PI3K signaling, leading IL-4 secretion, acts an autocrine manner further promote polarization. Interestingly, these stiffened microenvironments also suppressed proinflammatory response. In coculture experiments with breast lines (MDA-MB-231 MCF-7), macrophages within significantly proliferation invasion. These findings suggest its create more favorable environment for modulating activity. Overall, our study underscores critical role ECM mechanics shaping immune TME, highlighting potential therapies target inhibit enhance efficacy.

Language: Английский

Citations

0