Tug of war: Understanding the dynamic interplay of tumor biomechanical environment on dendritic cell function

Quartey, Brian Chesney; Torres, Gabriella; ElGindi, Mei; Alatoom, Aseel; Sapudom, Jiranuwat; Teo, Jeremy CM

doi:10.1016/j.mbm.2024.100068

Cited by 2 publications

References 189 publications

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Application of Nanomaterials in the Repair and Regeneration of Lymphatic Organs and Corresponding Biophysical Simulation Strategies

Liu,

Wang

2024

Advanced NanoBiomed Research

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

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Application of Nanomaterials in the Repair and Regeneration of Lymphatic Organs and Corresponding Biophysical Simulation Strategies

Liu,

Wang

2024

Advanced NanoBiomed Research

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Mechano-mediated M2 macrophage polarization and immune suppression in stiffened tumor microenvironment

Sapudom,

Tipay,

Teo

2024

Preprint

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

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Tug of war: Understanding the dynamic interplay of tumor biomechanical environment on dendritic cell function

Cited by 2 publications

References 189 publications

Application of Nanomaterials in the Repair and Regeneration of Lymphatic Organs and Corresponding Biophysical Simulation Strategies

Application of Nanomaterials in the Repair and Regeneration of Lymphatic Organs and Corresponding Biophysical Simulation Strategies

Mechano-mediated M2 macrophage polarization and immune suppression in stiffened tumor microenvironment

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