Single-Cell RNA Sequencing of Lymph Node Stromal Cells Reveals Niche-Associated Heterogeneity

Rodda, Lauren B.; Lu, Erick; Bennett, Mariko L.; Sokol, Caroline L.; Wang, Xiaoming; Luther, Sanjiv A.; Barres, Ben A.; Luster, Andrew D.; Ye, Chun Jimmie; Cyster, Jason G.

doi:10.1016/j.immuni.2018.04.006

Cited by 361 publications

(575 citation statements)

References 81 publications

(121 reference statements)

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“…The complexity of the lymph node stroma was highlighted in a recent comprehensive paper which identified nine distinct subsets of non‐endothelial stromal cells based on single‐cell RNA‐seq data from mouse lymph nodes . This included several subsets of FRCs and emphasises the importance of considering the lymph node as a distinct tumour microenvironment compared to that found in the oral cavity.…”

Section: Lymph Node Metastasismentioning

confidence: 99%

“…However, the impact of FRCs on tumour cells and their development once they reach the lymph node is unknown. In addition, multiple subtypes of FRC have now been identified within the lymph node localised to specific areas within the cortex or subcapsular synapse, suggesting that more detailed analysis of FRC subset responses may be needed to understand their role in the different stages of lymph node metastases development.…”

Section: The Tumour Microenvironment In Enementioning

confidence: 99%

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Extranodal extension in oral cancer: A role for the nodal microenvironment?

Pilborough

Lambert

Khurram

2019

J Oral Pathology Medicine

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Oral squamous cell carcinoma (OSCC) is a significant cause of morbidity and mortality worldwide and accounts for the majority of head and neck cancers. Metastasis of primary tumours, primarily to cervical lymph nodes in the neck, is associated with worsening prognosis. Furthermore, the prognosis of patients with extranodal extension of metastatic tumour from the lymph nodes into the neck tissues is particularly poor. The factors affecting this process are poorly understood, and detection is difficult pre‐surgery. Mounting evidence shows that components of the tumour microenvironment including cancer‐associated fibroblasts, vascular and lymphatic endothelial cells, the extracellular matrix and inflammatory immune cells, are important modulators of tumour behaviour in primary OSCC and other cancers. However, little is known about the lymph node microenvironment, its response to tumour presence and role in extranodal extension. In addition, there are many lymph node‐specific cell types and structures, such as fibroblast reticular cells and high endothelial venules, making the lymph node microenvironment distinct from that found at primary tumour sites, and which contribute to the nodal response to tumour presence. This review details the current knowledge regarding the lymph node tumour microenvironment in OSCC and its role in lymph node metastasis and extranodal extension and relates this to features of the primary tumour. Understanding the role that the lymph node microenvironment plays in promoting tumour development and extranodal extension may aid the identification of novel biomarkers and alternative treatment strategies to improve the prognosis of patients with advanced OSCC.

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Section: Lymph Node Metastasismentioning

confidence: 99%

Section: The Tumour Microenvironment In Enementioning

confidence: 99%

Extranodal extension in oral cancer: A role for the nodal microenvironment?

Pilborough

Lambert

Khurram

2019

J Oral Pathology Medicine

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“…The concept of stromal cells as active contributors to immunity and inflammation grew from studies of the nonhaematopoietic cellular compartment of secondary lymphoid organs. From the first identification of a lymph node stromal cell subset (gp38‐expressing fibroblastic reticular cells) in 1992, the field has developed significantly, with at least 10 distinct subsets of stromal cells now identified in the lymph node alone . Stromal cells play a critical role in the initiation of both homoeostatic and inflammatory lymphoid tissue development, as well as having an array of direct and indirect effects on haematopoietic immune cells .…”

Section: Stromal Cells: Active Contributors To Immunity and Inflammationmentioning

confidence: 99%

The oncostatin M‐stromal cell axis in health and disease

West¹,

Owens

Hegazy

2018

Scand J Immunol

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The field of stromal immunology has risen to prominence in the last decade, fuelled by accumulating evidence that nonhaematopoietic mesenchymal cells are not simply involved in modulating tissue structure, but actively contribute to immune processes. In addition to regulating tissue integrity during homoeostasis, stromal cells are sensitive sensors of inflammatory stimuli produced downstream of tissue injury or infection, and respond by producing a wide variety of chemokines, cytokines and adhesion factors that contribute to immunity and tissue repair. When not appropriately regulated, these same processes can result in inflammatory pathology and organ dysfunction. In this review, we provide a brief overview of stromal immunology, followed by a comprehensive discussion of how the IL-6 family cytokine oncostatin M (OSM) coordinates stromal cell activity in diverse physiological and pathological contexts. We conclude by providing a perspective on the potential clinical value of the OSM-stromal cell axis and how this pathway might be exploited therapeutically.

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“…107,108 Laminins are a family of extracellular matrix components expressed on basement membranes. 106,111,112 In LN, laminin α4 106,111,112 In LN, laminin α4…”

Section: Lymph Node Microenvironment: Stromal Fibers and Conduitsmentioning

confidence: 99%

Role of lymph node stroma and microenvironment in T cell tolerance

Saxena

Paluskievicz

et al. 2019

Immunological Reviews

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Lymph nodes (LNs) are at the cross roads of immunity and tolerance. These tissues are compartmentalized into specialized niche areas by lymph node stromal cells (LN SCs). LN SCs shape the LN microenvironment and guide immunological cells into different zones through establishment of a CCL19 and CCL21 gradient. Following local immunological cues, LN SCs modulate activity to support immune cell priming, activation, and fate. This review will present our current understanding of LN SC subsets roles in regulating T cell tolerance. Three major types of LN SC subsets, namely fibroblastic reticular cells, lymphatic endothelial cells, and blood endothelial cells, are discussed. These subsets serve as scaffolds to support and regulate T cell homeostasis. They contribute to tolerance by presenting peripheral tissue antigens to both CD4 and CD8 T cells. The role of LN SCs in regulating T cell migration and tolerance induction is discussed. Looking forward, recent advances in bioengineered materials and approaches to leverage LN SCs to induce T cell tolerance are highlighted, as are current clinical practices that allow for manipulation of the LN microenvironment to induce tolerance. Increased understanding of LN architecture, how different LN SCs integrate immunological cues and shape immune responses, and approaches to induce T cell tolerance will help further combat autoimmune diseases and graft rejection.

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Single-Cell RNA Sequencing of Lymph Node Stromal Cells Reveals Niche-Associated Heterogeneity

Cited by 361 publications

References 81 publications

Extranodal extension in oral cancer: A role for the nodal microenvironment?

Extranodal extension in oral cancer: A role for the nodal microenvironment?

The oncostatin M‐stromal cell axis in health and disease

Role of lymph node stroma and microenvironment in T cell tolerance

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