Publications by authors named "Lin-Zhou Zhang"

Background: Venous malformations (VMs), predominantly arising from activating mutations of tyrosine kinase receptor TIE2 within endothelial cells (ECs), are characterized by dilated and tortuous vessels with a paucity of perivascular cells. The mechanisms of interaction between mutant ECs and perivascular cells remain largely elusive.

Objectives: To investigate the characteristics of extracellular vesicles (EVs) from VM ECs, especially their carried miRNAs and their roles in the crosstalk between ECs and perivascular cells in VM pathogenesis.

View Article and Find Full Text PDF

Malignancies can compromise systemic innate immunity, but the underlying mechanisms are largely unknown. Here, we find that tumor-derived small extracellular vesicles (sEVs; TEVs) deliver PD-L1 to host macrophages, thereby impeding antibacterial immunity. Mice implanted with Rab27a-knockdown tumors are more resistant to bacterial infection than wild-type controls.

View Article and Find Full Text PDF
Article Synopsis
  • * Research found that NSCLC patients with mutations had higher levels of circulating PD-L1-positive small extracellular vesicles (sEVs), which negatively affected CD8 T cell functionality in tumor tissues.
  • * The study identified that both mutation-induced and TKI treatment-induced increases in PD-L1-positive sEVs occur through different molecular pathways (HRS and ALIX), potentially explaining the limited response to immunotherapy in these patients.
View Article and Find Full Text PDF
Article Synopsis
  • Only a small number of cancer patients benefit from immune checkpoint blockade therapy due to complex interactions among immune checkpoint pathways and molecules in circulating small extracellular vesicles (sEVs).
  • The study found that PD-1 and CD80 on immunocyte-derived sEVs lead to reduced PD-L1 on tumor cell membranes while increasing PD-L1 secretion, contributing to systemic immunosuppression and making tumors less responsive to immune attacks.
  • Analyzing multiple checkpoint molecules on circulating sEVs can help differentiate between patients who will respond well to anti-PD-1 treatments and those who will not, highlighting a potential target for improving cancer therapies.
View Article and Find Full Text PDF

Objectives: Ameloblastoma (AM), a locally aggressive tumor with extensive growth capacity, causes significant damage to the jaw and affects facial appearance. Although the high prevalence of BRAF V600E mutation in AM is known, its specific impacts on patients with AM remain unclear. Thus, the present study investigated the role of BRAF V600E mutation, thereby focusing on its impact on AM invasion and growth.

View Article and Find Full Text PDF

Liquid biopsy is of great significance in tumor early diagnosis and treatment stratification. PD-L1-positive small extracellular vesicles (PD-L1 sEVs) are closely related to tumor growth and immunotherapy response, which are considered valuable liquid biopsy biomarkers. In contrast to conventional detection, detection has the ability to improve the detection efficiency and enable continuous or real-time dynamic monitoring.

View Article and Find Full Text PDF
Article Synopsis
  • Oral squamous cell carcinoma (OSCC) is a common and aggressive type of head and neck cancer that often spreads to lymph nodes; this study focuses on the role of the Ras-related protein Rab-27A (RAB27A) in its progression.
  • RAB27A was found to be overexpressed in OSCC tissues and metastatic lymph nodes, correlating with worse clinical outcomes and poorer survival rates; silencing this protein reduced cancer cell growth and spread in lab experiments.
  • The research also linked RAB27A to the epidermal growth factor receptor (EGFR) signaling pathway, suggesting it could be a promising target for new treatments against OSCC.
View Article and Find Full Text PDF

Background: The PD-L1 on tumor cell-derived small extracellular vesicles (sEVs) can suppress the proliferation and cytokine production of T cells. However, PD-L1 can also be expressed by non-tumor cells. The present study is designed to test whether immunocytes release immunosuppressive PD-L1-positive sEVs.

View Article and Find Full Text PDF

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V EGFR EVs and Annexin V EGFR EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique.

View Article and Find Full Text PDF

PD-L1 localized to immunosuppressive small extracellular vesicles (sEV PD-L1) contributes to tumor progression and is associated with resistance to immune-checkpoint blockade (ICB) therapy. Here, by establishing a screening strategy with a combination of tissue microarray (TMA), IHC staining, and measurement of circulating sEV PD-L1, we found that the endosomal sorting complex required for transport (ESCRT) member protein hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) was the key regulator of circulating sEV PD-L1 in head and neck squamous cell carcinoma (HNSCC) patients. Increased HRS expression was found in tumor tissues and positively correlated with elevated circulating sEV PD-L1 in patients with HNSCC.

View Article and Find Full Text PDF

Venous malformations (VMs), featuring localized dilated veins, are the most common developmental vascular anomalies. Aberrantly organized perivascular extracellular matrix (ECM) is one of the prominent pathological hallmarks of VMs, accounting for vascular dysfunction. Although previous studies have revealed various proteins involved in ECM remodeling, the detailed pattern and molecular mechanisms underlying the endothelium-ECM interplay have not been fully elucidated.

View Article and Find Full Text PDF

Anti-PD-1/PD-L1 immunotherapy has achieved impressive therapeutic outcomes in patients with multiple cancer types. However, the underlined molecular mechanism(s) for moderate response rate (15-25%) or resistance to PD-1/PD-L1 blockade remains not completely understood. Here, we report that inhibiting the deubiquitinase, USP8, significantly enhances the efficacy of anti-PD-1/PD-L1 immunotherapy through reshaping an inflamed tumor microenvironment (TME).

View Article and Find Full Text PDF

Leukocyte‑derived microparticles (LMPs) include neutrophil‑, lymphocyte‑ and monocyte‑derived MPs. LMPs act as proinflammatory mediators in autoimmune diseases, infectious diseases and vascular diseases. The present study examined the hypothesis that the percentage of LMPs was increased in patients with inflamed odontogenic keratocysts (OKCs), and investigated the biological effects of Jurkat cell‑derived MPs on the fibroblasts of OKCs in vitro.

View Article and Find Full Text PDF

Aims: The purpose of this study was to explore the potential involvement of Fra-1, c-Jun and c-Fos, three vital members of the AP-1 complex, in the pathogenesis of odontogenic keratocysts (OKCs).

Methods And Results: Tissue samples, containing 10 normal oral mucosa (OM), 10 dentigerous cysts (DC) and 32 OKC specimens, were applied to investigate the expression levels of Fra-1, c-Jun and c-Fos by immunohistochemistry and real-time-quantitative polymerase chain reaction (RT-qPCR). The association between Fra-1, c-Jun and c-Fos expression levels and markers of proliferation [Ki-67, proliferating cell nuclear antigen (PCNA)], anti-apoptosis (Bcl-2) was then investigated in the OKC serial tissue sections.

View Article and Find Full Text PDF