Background: Tumor immune microenvironment (TIM) plays a critical role in tumorigenesis and progression. Recently, therapies based on modulating TIM have made great breakthroughs in cancer treatment. Polo-like kinase 1 (PLK1) is a crucial regulatory factor of the cell cycle process and its dysregulations often cause various pathological processes including tumorigenesis. However, the detailed mechanisms surrounding the regulation of PLK1 on glioma immune microenvironment remain undefined.
Methods: Public databases and online datasets were used to extract data of PLK1 expression, clinical features, genetic alterations, and biological functions. The EdU, flow cytometry, and macrophage infiltration assays as well as xenograft animal experiments were performed to determine the relationship between PLK1 and glioma immune microenvironment and .
Results: PLK1 is always highly expressed in multiple cancers especially in glioma. Univariable and Multivariate proportional hazard Cox analysis showed that PLK1 was a prognostic biomarker for glioma. Simultaneously, highly expressed PLK1 is significantly related to prognosis, histological and genetic features in glioma by analyzing public databases. In addition, the enrichment analysis suggested that PLK1 might related to "immune response", "cell cycle", "DNA replication", and "mismatch repair" in glioma. Immune infiltration analysis demonstrated that highly expressed PLK1 inhibited M1 macrophages infiltration to glioblastoma immune microenvironment by Quantiseq and Xcell databases and negatively related to some chemokines and marker genes of M1 macrophages in glioblastoma. Subsequent experiments confirmed that PLK1 knockdown inhibited the proliferation of glioma cells but increased the M1 macrophages infiltration and polarization. Furthermore, in glioma xenograft mouse models, we showed that inhibiting PLK1 blocked tumor proliferation and increased the M1 macrophages infiltration. Finally, PLK1 methylation analysis and lncRNA-miRNA network revealed the potential mechanism of abnormal PLK1 expression in glioma.
Conclusions: PLK1 inhibits M1 macrophages infiltration into glioma immune microenvironment and is a potential biomarker for glioma.
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http://dx.doi.org/10.3389/fimmu.2022.1058036 | DOI Listing |
ACS Infect Dis
January 2025
Department of Microbiology, Genetics, and Immunology, Michigan State University, East Lansing, Michigan 48824, United States.
Group B (GBS) is a major cause of fetal and neonatal mortality worldwide. Many of the adverse effects of invasive GBS are associated with inflammation; therefore, understanding bacterial factors that promote inflammation is of critical importance. Membrane vesicles (MVs), which are produced by many bacteria, may modulate host inflammatory responses.
View Article and Find Full Text PDFHepatol Commun
November 2024
Department of Pathology, University of Illinois Chicago, Chicago, Illinois, USA.
Background: We previously identified that high-mobility group box-1 (HMGB1) is increased and undergoes post-translational modifications (PTMs) in response to alcohol consumption. Here, we hypothesized that specific PTMs, occurring mostly in hepatocytes and myeloid cells, could contribute to the pathogenesis of alcohol-associated liver disease (AALD).
Methods: We used the Lieber-DeCarli (LD) model of early alcohol-induced liver injury, combined with engineered viral vectors and genetic approaches to regulate the expression of HMGB1, its PTMs (reduced [H], oxidized [O], acetylated [Ac], both [O + Ac]), and its receptors (RAGE, TLR4) in a cell-specific manner (hepatocytes and/or myeloid cells).
Bioact Mater
April 2025
School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, PR China.
Complete spinal cord injury (SCI) causes permanent locomotor, sensory and neurological dysfunctions. Targeting complex immunopathological microenvironment at SCI sites comprising inflammatory cytokines infiltration, oxidative stress and massive neuronal apoptosis, the conductive oriented nanofiber felt with efficient ROS clearance, anti-inflammatory effect and accelerating neural regeneration is constructed by step-growth addition polymerization and electrostatic spinning technique for SCI repair. The formation of innovative Fe-PDA-PAT chelate in nanofiber felt enhances hydrophilic, antioxidant, antibacterial, hemostatic and binding factor capacities, thereby regulating immune microenvironment of SCI.
View Article and Find Full Text PDFBioact Mater
March 2025
Tianjin Key Laboratory of Spine and Spinal Cord, International Science and Technology Cooperation Base of Spinal Cord Injury, Department of Orthopedics, International Chinese Musculoskeletal Research Society Collaborating Center for Spinal Cord Injury, Tianjin Medical University General Hospital, Tianjin, 300070, China.
Spinal cord injury triggers leukocyte mobilization from the peripheral circulation to the injury site, exacerbating spinal cord damage. Simultaneously, bone marrow hematopoietic stem cells (HSCs) and splenic leukocytes rapidly mobilize to replenish the depleted peripheral blood leukocyte pool. However, current treatments for spinal cord injuries overlook interventions targeting peripheral immune organs and tissues, highlighting the need to develop novel drugs capable of effectively regulating peripheral immunity and treating spinal cord injuries.
View Article and Find Full Text PDFAging Cell
January 2025
School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
Accumulation of damaged biomolecules in body tissues is the primary cause of aging and age-related chronic diseases. Since this damage often occurs spontaneously, it has traditionally been regarded as untreatable, with typical therapeutic strategies targeting genes or enzymes being ineffective in this domain. In this report, we demonstrate that an antibody targeting the isoDGR damage motif in lung tissue can guide immune clearance of harmful damaged proteins in vivo, effectively reducing age-linked lung inflammation.
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