3D Collagen Fiber Concentration Regulates Treg Cell Infiltration in Triple Negative Breast Cancer

Gao, Huan; Tian, Qiang; Zhou, Yan; Zhu, Lizhe; Lu, Yinliang; Ma, Yingying; Feng, Jinteng; Jiang, Yongchao; Wang, Bo

doi:10.3389/fimmu.2022.904418

Cited by 10 publications

(8 citation statements)

References 39 publications

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“…This decrease in the proliferation of activated T-cells correlated well with the previously discussed activation states of T-cells ( Figure 4A-C ). Our finding is in agreement with another study that demonstrated that increased collagen density can diminish T-cell proliferation [11, 62]. Conversely, a study using 3D alginate hydrogels revealed enhanced T-cell proliferation in stiffer hydrogels [22].…”

Section: Resultssupporting

confidence: 93%

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: Resultssupporting

confidence: 93%

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

Sapudom,

Alatoom,

Tipay

et al. 2024

Preprint

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“…Moreover, the ECM stiffness was shown to modulate the phenotype of CD4+ and CD8+ cells in the same study. In parallel, 3D collagen gels evidenced that increased collagen concentrations promoted the infiltration of regulatory T cells, in agreement with the altered ECM signaling correlated with T reg content in breast cancers [ 106 ].…”

Section: Future Is Coming Giving a New Dimension To The Tradementioning

confidence: 77%

A Bloody Conspiracy— Blood Vessels and Immune Cells in the Tumor Microenvironment

Terrassoux

Claux

Bacari

et al. 2022

Cancers

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Cancer progression occurs in concomitance with a profound remodeling of the cellular microenvironment. Far from being a mere passive event, the re-orchestration of interactions between the various cell types surrounding tumors highly contributes to the progression of the latter. Tumors notably recruit and stimulate the sprouting of new blood vessels through a process called neo-angiogenesis. Beyond helping the tumor cope with an increased metabolic demand associated with rapid growth, this also controls the metastatic dissemination of cancer cells and the infiltration of immune cells in the tumor microenvironment. To decipher this critical interplay for the clinical progression of tumors, the research community has developed several valuable models in the last decades. This review offers an overview of the various instrumental solutions currently available, including microfluidic chips, co-culture models, and the recent rise of organoids. We highlight the advantages of each technique and the specific questions they can address to better understand the tumor immuno-angiogenic ecosystem. Finally, we discuss this development field’s fundamental and applied perspectives.

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“…Blocking immune cell expression in the tumor microenvironment and preventing their full role can lead to tumor development and metastasis. While internal genetic changes primarily lead to tumor cell formation, the tumor microenvironment, in ammatory processes, and immune response play crucial roles in tumor progression [11]. Sokratos [12] found that the tumor stroma plays a critical role in tumor occurrence, development, invasion, metastasis, and treatment sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Identifying immune cell infiltration and diagnostic biomarkers for nasopharyngeal carcinoma through bioinformatic analysis

zhao,

Qiu,

2024

Preprint

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Backgrounds: Explore the genomic and signaling pathways contributing to nasopharyngeal carcinoma, a prevalent and multifactorial cancer involving environmental, genetic, and EB virus factors. This study aims to identify potential genes associated with nasopharyngeal cancer and examine their relationship with immune cell infiltration. Methods: The Gene Expression Omnibus (GEO) database provided three sets of nasopharyngeal cancer data: two for training and one for validation. To identify candidate genes, a Protein-Protein Interaction (PPI) network was constructed using a string database and two machine learning algorithms: the Least Absolute Selection and Shrinkage Operator (LASSO) and the Supporting Vector Machine Resource Elimination (SVM-RFE). The external validation dataset assessed the proposed levels of expression of biomarkers and the diagnostic value of the test to evaluate its effectiveness. Receiver Operating Characteristic (ROC) curves were used to measure diagnostic performance, convolutional techniques in CIBERSORT were applied for immune cell infiltration analysis, and correlation analysis was conducted using the training dataset. Results: The GEO database provided GSE12452 and GSE13597 datasets. The limma package filtered 58 differential genes, including 13 upregulated and 35 downregulated genes, which were visualized using volcano maps, heat maps, and PCA. Enrichment analysis results indicated a significant association between inflammation and disease. The Lasso and SVM algorithms were applied to screen 9 and 37 differential genes, respectively. Overlapping genes associated with nasopharyngeal cancer include ATP12A, LAMB1, RAD51AP1, CXCL11, BINSM1, PTGS2, and SAA1. Their diagnostic significance was confirmed using the operational characteristic Receptor of the validation group, and they were found to be highly connected to the degree of immune cell infiltration. Conclusions: These seven genes are considered promising biomarkers for diagnosing nasopharyngeal cancer, paving the way for future research on the immunological mechanisms and therapy of nasopharyngeal carcinoma.

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3D Collagen Fiber Concentration Regulates Treg Cell Infiltration in Triple Negative Breast Cancer

Cited by 10 publications

References 39 publications

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

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

A Bloody Conspiracy— Blood Vessels and Immune Cells in the Tumor Microenvironment

Identifying immune cell infiltration and diagnostic biomarkers for nasopharyngeal carcinoma through bioinformatic analysis

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