iScience
Translational Oncology Group, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, Germany.
Published: December 2023
A crucial requirement for metastasis formation in ovarian high-grade serous carcinoma (HGSC) is the disruption of the protective peritoneal mesothelium. Using co-culture systems of primary human cells, we discovered that tumor-associated NK cells induce TRAIL-dependent apoptosis in mesothelial cells via death receptors DR4 and DR5 upon encounter with activated T cells. Upregulation of TRAIL expression in NK cells concomitant with enhanced cytotoxicity toward mesothelial cells was driven predominantly by T-cell-derived TNFα, as shown by affinity proteomics-based analysis of the T cell secretome in conjunction with functional studies. Consistent with these findings, we detected apoptotic mesothelial cells in the peritoneal fluid of HGSC patients. In contrast to mesothelial cells, HGSC cells express negligible levels of both DR4 and DR5 and are TRAIL resistant, indicating cell-type-selective killing by NK cells. Our data point to a cooperative action of T and NK in breaching the mesothelial barrier in HGSC patients.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692662 | PMC |
http://dx.doi.org/10.1016/j.isci.2023.108401 | DOI Listing |
J Exp Med
February 2025
Immunology Department, Unit of Lymphocytes and Immunity, Institut Pasteur, Paris, France.
Embryonic hematopoietic cells develop in the fetal liver (FL), surrounded by diverse non-hematopoietic stromal cells. However, the spatial organization and cytokine production patterns of the stroma during FL development remain poorly understood. Here, we characterized and mapped the hematopoietic and stromal cell populations at early (E12.
View Article and Find Full Text PDFPLoS One
January 2025
Trauma Research, Swedish Medical Center, Englewood, Colorado, United States of America.
Previous abdominal surgery (PAS) increases risk of small bowel obstruction (SBO) due to adhesions, and appendectomy (appy) is an independent risk factor for abdominal adhesion-related complications. Peritoneal inflammation, e.g.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Nephrology, Second Hospital of Jilin University, Changchun, China.
Long-term exposure of the peritoneum to peritoneal dialysate results in pathophysiological changes in the anatomical organization of the peritoneum and progressive development of peritoneal fibrosis. This leads to a decline in peritoneal function and ultrafiltration failure, ultimately necessitating the discontinuation of peritoneal dialysis, severely limiting the potential for long-term maintenance. Additionally, encapsulating peritoneal sclerosis, a serious consequence of peritoneal fibrosis, resulting in patients discontinuing PD and significant mortality.
View Article and Find Full Text PDFCancer Med
January 2025
Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Clinical Medicine, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia.
Objective: Endometrial cancer is one of the few cancers for which mortality is still increasing. A lack of treatment options remains a major challenge, particularly for some subtypes of the disease. GZD824, also known as olverembatinib, is a multi-kinase inhibitor previously investigated in clinical trials for chronic myeloid leukaemia and Ph+ acute lymphoblastic leukaemia as a BCR-ABL inhibitor.
View Article and Find Full Text PDFMar Drugs
November 2024
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Peritoneal dialysis (PD) serves as a home-based kidney replacement therapy with increasing utilization across the globe. However, long-term use of high-glucose-based PD solution incites repeated peritoneal injury and inevitable peritoneal fibrosis, thus compromising treatment efficacy and resulting in ultrafiltration failure eventually. In the present study, we utilized human mesothelial MeT-5A cells for the in vitro experiments and a PD mouse model for in vivo validation to study the pathophysiological mechanisms underneath PD-associated peritoneal fibrosis.
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.