Single-Cell Transcriptomic Profiles of Lung Pre-Metastatic Niche Reveal Neutrophil and Lymphatic Endothelial Cell Roles in Breast Cancer

Huang, Yu‐Tung; Chang, Chao‐Yuan; Wu, Yu‐Yuan; Wu, Kwou-Yeung; Tsai, Yu-Chen; Lee, Hsiao-Chen; Tsai, Eing‐Mei; Hsu, Ya‐Ling

doi:10.3390/cancers15010176

Cited by 4 publications

(2 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, CD11b+Ly6G+ immune cells are reported to inhibit CD8+ T cell functions and facilitate breast cancer metastasis 42 . Neutrophils also play a critical role in creating a pre-metastatic niche in the lung microenvironment and their reduction may contribute to a potentially less permissive environment for metastatic seeding and colonization in breast cancer 45,46 . The alterations in immune cell infiltrates, such as increased CD8+ T cells, B cells with reduced PD-L1 expression, and decreased neutrophils suggest that iEF treatment hinders metastasis by orchestrating changes in the immune landscape of the lung microenvironment.…”

Section: Resultsmentioning

confidence: 99%

Induced electric fields inhibit breast cancer growth and metastasis by modulating the immune tumor microenvironment

Charan,

Jones,

Ahirwar

et al. 2024

Preprint

View full text Add to dashboard Cite

Despite tremendous advances in oncology, metastatic triple-negative breast cancer remains difficult to treat and manage with established therapies. Here, we show in mice with orthotopic triple-negative breast tumors that alternating (100 kHz), and low intensity (<1 mV/cm) induced electric fields (iEFs) significantly reduced primary tumor growth and distant lung metastases. Non-contact iEF treatment can be delivered safely and non-invasively in vivo via a hollow, rectangular solenoid coil. We discovered that iEF treatment enhances anti-tumor immune responses at both the primary breast and secondary lung sites. In addition, iEF reduces immunosuppressive TME by reducing effector CD8+ T cell exhaustion and the infiltration of immunosuppressive immune cells. Furthermore, iEF treatment reduced lung metastasis by increasing CD8+ T cells and reducing immunosuppressive Gr1+ neutrophils in the lung microenvironment. We also observed that iEFs reduced the metastatic potential of cancer cells by inhibiting epithelial-to-mesenchymal transition. By introducing a non-invasive and non-toxic electrotherapeutic for inhibiting metastatic outgrowth and enhancing anti-tumor immune response in vivo, treatment with iEF technology could add to a paradigm-shifting strategy for cancer therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

Induced electric fields inhibit breast cancer growth and metastasis by modulating the immune tumor microenvironment

Charan,

Jones,

Ahirwar

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…This leads to the recruitment of neutrophils with high levels of C3a receptors to pre-metastatic niche, supporting metastasis [ 34 ]. Huang et al identified a group of lymphatic endothelial cells (EC) with increased Ki67 and S100A6 expression,which impaired EC tight junction and increased the transendothelial migration of neutrophils [ 35 ].…”

Section: Neutrophil Chemotaxis Towards Pre-metastatic Nichementioning

confidence: 99%

The role and metabolic adaptations of neutrophils in premetastatic niches

Chen

2023

Biomark Res

View full text Add to dashboard Cite

It has been found that tumor cells create microenvironments in distant organs that promote their survival and growth in advance of their arrival. These predetermined microenvironments are referred to as “pre-metastatic niches”. Increasing attention is being paid to neutrophils’ role in forming the pre-metastatic niche. As major components of the pre-metastatic niche, tumor-associated neutrophils (TANs) play an important role in the formation of the pre-metastatic niche through communication with multiple growth factors, chemokines, inflammatory factors, and other immune cells, which together create a pre-metastatic niche well suited for tumor cell seeding and growth. However, how TANs modulate their metabolism to survive and exert their functions in the process of metastasis remains largely to be discovered. Accordingly, the objective of this review is to assess the role that neutrophils play in the formation of pre-metastatic niche and to explore the metabolism alteration of neutrophils in cancer metastasis. A better understanding of the role of TANs in pre-metastatic niche will help us discover new mechanisms of metastasis and develop new therapies targeting TANs.

show abstract

Single‐Cell RNA Sequencing and Spatial Transcriptomics Reveal Pathogenesis of Meningeal Lymphatic Dysfunction after Experimental Subarachnoid Hemorrhage

Wang,

Zhang,

et al. 2023

Advanced Science

View full text Add to dashboard Cite

Subarachnoid hemorrhage (SAH) is a devastating subtype of stroke with high mortality and disability rate. Meningeal lymphatic vessels (mLVs) are a newly discovered intracranial fluid transport system and are proven to drain extravasated erythrocytes from cerebrospinal fluid into deep cervical lymph nodes after SAH. However, many studies have reported that the structure and function of mLVs are injured in several central nervous system diseases. Whether SAH can cause mLVs injury and the underlying mechanism remain unclear. Herein, single‐cell RNA sequencing and spatial transcriptomics are applied, along with in vivo/vitro experiments, to investigate the alteration of the cellular, molecular, and spatial pattern of mLVs after SAH. First, it is demonstrated that SAH induces mLVs impairment. Then, through bioinformatic analysis of sequencing data, it is discovered that thrombospondin 1 (THBS1) and S100A6 are strongly associated with SAH outcome. Furthermore, the THBS1‐CD47 ligand‐receptor pair is found to function as a key role in meningeal lymphatic endothelial cell apoptosis via regulating STAT3/Bcl‐2 signaling. The results illustrate a landscape of injured mLVs after SAH for the first time and provide a potential therapeutic strategy for SAH based on mLVs protection by disrupting THBS1 and CD47 interaction.

show abstract

Single-Cell Transcriptomic Profiles of Lung Pre-Metastatic Niche Reveal Neutrophil and Lymphatic Endothelial Cell Roles in Breast Cancer

Cited by 4 publications

References 49 publications

Induced electric fields inhibit breast cancer growth and metastasis by modulating the immune tumor microenvironment

Induced electric fields inhibit breast cancer growth and metastasis by modulating the immune tumor microenvironment

The role and metabolic adaptations of neutrophils in premetastatic niches

Single‐Cell RNA Sequencing and Spatial Transcriptomics Reveal Pathogenesis of Meningeal Lymphatic Dysfunction after Experimental Subarachnoid Hemorrhage

Contact Info

Product

Resources

About