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Inhibitory cell-surface receptors on lymphocytes, often called immune checkpoints, are powerful targets for cancer therapy. Despite their direct involvement in autoimmune pathology, they are currently not exploited therapeutically for autoimmune diseases. Understanding the expression pattern of these receptors in health and disease is essential for targeted drug design. Here, we designed three 23-colour flow cytometry panels for peripheral-blood T cells, including 15 lineage-defining markers and 21 immunomodulatory cell-surface receptors, and a 22-marker panel for B cells. Blood samples from healthy individuals, multiple sclerosis (MS), and lupus (SLE) patients were included in the study. Several receptors show differential expression on regulatory T cells (Treg) compared to T helper (Th) 1 and Th17 cells, and functional relevance of this difference could be shown for BTLA and CD5. Unbiased multiparametric analysis revealed a subset of activated CD8 T cells and a subset of unswitched memory B cells that are diminished in MS and SLE, respectively.
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http://dx.doi.org/10.1016/j.clim.2019.108276 | DOI Listing |
Nature
September 2025
Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Key Laboratory of RNA Innovation Science and Engineering, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Antigen-induced clustering of cell surface receptors, including T cell receptors and Fc receptors, represents a widespread mechanism in cell signalling activation. However, most naturally occurring antigens, such as tumour-associated antigens, stimulate limited receptor clustering and on-target responses owing to insufficient density. Here we repurpose proximity labelling, a method used to biotinylate and identify spatially proximal proteins, to amplify designed probes as synthetic antigen clusters on the cell surface.
View Article and Find Full Text PDFBiol Pharm Bull
September 2025
Department of Intensive Care Unit, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310007, China.
Ferroptosis is involved in the progression of sepsis-induced acute lung injury (ALI). Kaempferol is a flavonoid compound that can protect against ALI. 5-Methylcytosine (m5C) is involved in the pathogenesis of sepsis.
View Article and Find Full Text PDFJ Immunother Cancer
September 2025
Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA
Background: Tumor heterogeneity and antigen escape are mechanisms of resistance to chimeric antigen receptor (CAR)-T cell therapy, especially in solid tumors. Targeting multiple antigens with a unique CAR construct could be a strategy for a better tumor control than monospecific CAR-T cells on heterogeneous models. To overcome tumor heterogeneity, we targeted mesothelin (meso) and Mucin 16 (MUC16), two antigens commonly expressed in solid tumors, using a tandem CAR design.
View Article and Find Full Text PDFJ Immunother Cancer
September 2025
Division of Hematology & Oncology, Department of Medicine, School of Medicine, University of California, Irvine, California, USA
Background: γδ T cells possess unique immunological features including tissue tropism, major histocompatibility complex-independent antigen recognition, and hybrid T/natural killer cell properties that make them promising candidates for cancer immunotherapy. However, the therapeutic potential of Vδ1 γδ T cells, particularly when engineered with chimeric antigen receptors (CARs), remains underexplored in solid tumors such as pancreatic cancer (PC), largely due to their low abundance in peripheral blood and challenges in ex vivo expansion. This study aims to directly compare the preclinical safety and efficacy among CAR-engineered Vδ1 γδ T cells, Vδ2 γδ T cells, and conventional αβ T cells.
View Article and Find Full Text PDFBMJ Case Rep
September 2025
Diabetes and Endocrinology, North West Anglia NHS Foundation Trust, Peterborough, Cambridgeshire, UK
Familial hypocalciuric hypercalcaemia (FHH) is a rare disorder that represents a minute but important part of the differential diagnosis of hypercalcaemia. We describe a man in his 60s who was re-referred to endocrinology because of hypercalcaemia thought to be due to primary hyperparathyroidism (PHPT) that had not been followed up for 13 years. In his early 50s, the hypercalcaemia was accompanied by normal serum parathyroid hormone (PTH) levels, normal 24-hour urinary calcium excretion and normal bone density and kidney imaging, and no parathyroid adenoma was demonstrated on neck imaging.
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