The T Cell Journey: A Tour de Force

Alatoom, Aseel; ElGindi, Mei; Sapudom, Jiranuwat; Teo, Jeremy C M

doi:10.1002/adbi.202200173

Cited by 8 publications

(2 citation statements)

References 179 publications

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“…As T-cells navigate through the body, they traverse a myriad of mechanical microenvironments, seamlessly transitioning from the bloodstream through the intricate network of blood vessels and into the complex, fibrillar structures of tissues. This journey is likely underpinned by the principle of cellular mechanotransduction [1][2][3], a process that enables T-cells to fine-tune their behavior, optimizing immunological responses and operational efficacy. Such adaptability is underscored by observations that T-cells alter their migration patterns in response to the diverse mechanical cues encountered across different tissue landscapes [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Matrix alignment and density modulate YAP-mediated T-cell immune suppression

Sapudom,

Alatoom,

Tipay

et al. 2024

Preprint

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T-cells navigate through various mechanical environments within the body, adapting their behavior in response to these cues. An altered extracellular matrix (ECM) characterized by increased density and enhanced fibril alignment, as observed in cancer tissues, can significantly impact essential T-cell functions critical for immune responses. In this study, we used 3D collagen matrices with controlled density and fibril alignment to investigate T-cell migration, activation, and proliferation. Our results revealed that dense and aligned collagen matrices suppress T-cell activation through enhanced YAP signaling. By inhibiting YAP signaling, we demonstrated that T-cell activation within these challenging microenvironments improved, suggesting potential strategies to enhance the efficacy of immunotherapy by modulating T-cell responses in dense and aligned ECMs. Overall, our study deepens our understanding of T-cell mechanobiology within 3D relevant cellular microenvironments and provides insights into countering ECM-induced T-cell immunosuppression in diseases such as cancer.

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Section: Introductionmentioning

confidence: 99%

Matrix alignment and density modulate YAP-mediated T-cell immune suppression

Sapudom,

Alatoom,

Tipay

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…As cancer progresses, the TME undergoes significant physical and biochemical changes, including excessive production of ECM components by cancer-associated fibroblasts (CAFs) [6,7] and ECM stiffening due to increased enzymatic cross-linking by lysyl oxidase and enhanced collagen fibril alignment [8][9][10]. These alterations collectively create a distinct mechanical microenvironment that impacts the behavior of cancer cells and stromal cells, especially immune cells and fibroblasts, by modulating their migration and activation within the TME [11,12]. For example, a stiffened ECM activates mechanotransduction pathways (e.g., the YAP/TAZ, Rho/ROCK, and cell nuclear deformation pathways), promoting cancer cell survival, proliferation, migration, and drug response [2,13,14].…”

Section: Introductionmentioning

confidence: 99%

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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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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The T Cell Journey: A Tour de Force

Cited by 8 publications

References 179 publications

Matrix alignment and density modulate YAP-mediated T-cell immune suppression

Matrix alignment and density modulate YAP-mediated T-cell immune suppression

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

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

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