Clin Transl Med
Institute of Systems Immunology, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany.
Published: April 2024
Background: IL-17A and TNF synergistically promote inflammation and tumorigenesis. Their interplay and impact on ovarian carcinoma (OC) progression are, however, poorly understood. We addressed this question focusing on mesothelial cells, whose interaction with tumor cells is known to play a pivotal role in transcoelomic metastasis formation.
Methods: Flow-cytometry and immunohistochemistry experiments were employed to identify cellular sources of IL-17A and TNF. Changes in transcriptomes and secretomes were determined by bulk and single cell RNA sequencing as well as affinity proteomics. Functional consequences were investigated by microscopic analyses and tumor cell adhesion assays. Potential clinical implications were assessed by immunohistochemistry and survival analyses.
Results: We identified Th17 cells as the main population of IL-17A- and TNF producers in ascites and detected their accumulation in early omental metastases. Both IL-17A and its receptor subunit IL-17RC were associated with short survival of OC patients, pointing to a role in clinical progression. IL-17A and TNF synergistically induced the reprogramming of mesothelial cells towards a pro-inflammatory mesenchymal phenotype, concomitantly with a loss of tight junctions and an impairment of mesothelial monolayer integrity, thereby promoting cancer cell adhesion. IL-17A and TNF synergistically induced the Th17-promoting cytokines IL-6 and IL-1β as well as the Th17-attracting chemokine CCL20 in mesothelial cells, indicating a reciprocal crosstalk that potentiates the tumor-promoting role of Th17 cells in OC.
Conclusions: Our findings reveal a novel function for Th17 cells in the OC microenvironment, which entails the IL-17A/TNF-mediated induction of mesothelial-mesenchymal transition, disruption of mesothelial layer integrity and consequently promotion of OC cell adhesion. These effects are potentiated by a positive feedback loop between mesothelial and Th17 cells. Together with the observed clinical associations and accumulation of Th17 cells in omental micrometastases, our observations point to a potential role in early metastases formation and thus to new therapeutic options.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10988119 | PMC |
http://dx.doi.org/10.1002/ctm2.1604 | DOI Listing |
Curr Res Food Sci
December 2024
Department of Immunology, College of Basic Medical Sciences, Jilin University, 126 Xin min Street, Changchun, 130021, China.
Inflammatory bowel disorders (IBD) can lead to severe complications like perforation, bleeding, and colon cancer, posing life-threatening risks. Murray ( Murr.), rich in polysaccharides, has been utilized in traditional diets for thousands of years.
View Article and Find Full Text PDFCancer Res
January 2025
Oregon Health & Science University, Portland, OR, United States.
Senescence is a non-proliferative, survival state that cancer cells can enter to escape therapy. In addition to soluble factors, senescence cells secrete extracellular vesicles (EVs), which are important mediators of intercellular communication. To explore the role of senescent cell-derived EVs (senEVs) in inflammatory responses to senescence, we developed an engraftment-based senescence model in wild-type mice and genetically blocked senEV release in vivo, without significantly affecting soluble mediators.
View Article and Find Full Text PDFPediatr Allergy Immunol
January 2025
Department of Microbiology, Immunology and Transplantation, Allergy and Immunology Research Group, KU Leuven, Leuven, Belgium.
Background: Type 1 regulatory T (Tr1) cells are critical players in maintaining peripheral tolerance, by producing high IL-10 levels in association with inducible T-cell co-stimulator (ICOS) expression. Whether these cells play a role in naturally acquired baked egg tolerance is unknown.
Objectives: Evaluate frequencies of egg-responsive Tr1 and Th2 cells in egg-allergic children that naturally acquired baked egg tolerance (BET) versus non-egg-allergic (NEA) children.
ACS Appl Mater Interfaces
January 2025
Center Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, P. R. China.
: Sjögren's syndrome (SS), an autoimmune disease, was characterized by sicca syndrome and systemic manifestations, presenting significant treatment challenges. Exosomes, naturally derived nanoparticles containing bioactive molecules, have garnered interest in regenerative medicine. The present study aimed to elucidate the immunoregulatory properties and mechanism of exosomes obtained from the stem cells derived from human exfoliated deciduous teeth (SHED-exos) in SS-induced sialadenitis.
View Article and Find Full Text PDFStaphylococcus aureus prosthetic joint infections (PJIs) are broadly considered incurable, and clinical diagnostics that guide conservative vs. aggressive surgical treatments do not exist. Multi-omics studies in a humanized NSG-SGM3 BLT mouse model demonstrate human T cells: 1) are remarkably heterogenous in gene expression and numbers, and 2) exist as a mixed population of activated, progenitor-exhausted, and terminally-exhausted Th1/Th17 cells with increased expression of immune checkpoint proteins (LAG3, TIM-3).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!
© LitMetric 2025. All rights reserved.