GRAIL (gene related to anergy in lymphocytes, also known as RNF128), an ubiquitin-protein ligase (E3), utilizes a unique single transmembrane protein with a split-function motif, and is an important gatekeeper of T-cell unresponsiveness. Although it may play a role in other CD4 T-cell functions including activation, survival and differentiation, GRAIL is most well characterized as a negative regulator of T-cell receptor responsiveness and cytokine production. Here, we review the recent literature on this remarkable E3 in the regulation of human and mouse CD4 T-cell unresponsiveness.
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http://dx.doi.org/10.1111/j.1742-4658.2010.07922.x | DOI Listing |
Cancer Metastasis Rev
January 2025
Research and Scientific Studies Unit, College of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia.
Lung cancer is a leading global cause of mortality, with non-small cell lung cancer (NSCLC) accounting for a significant portion of cases. Immune checkpoint inhibitors (ICIs) have transformed NSCLC treatment; however, many patients remain unresponsive. ICI resistance in NSCLC and its association with cellular plasticity, epithelial-mesenchymal transition (EMT), enhanced adaptability, invasiveness, and resistance is largely influenced by epigenetic changes, signaling pathways, tumor microenvironment, and associated immune cells, fibroblasts, and cytokines.
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November 2024
Agata Janowska, MD, Department of Dermatology, , University of Pisa, Via Roma 67, 56126, Pisa, Italy; Phone: +39 050 992436, Fax: +39 050 992556,
Mycosis fungoides (MF) represent the most frequent form of cutaneous T-cell lymphoma (CTCL). Chlormethine gel has been approved as first-line therapy in MF. The classification of early forms of MF is clinically and histologically complex even for experienced clinicians.
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December 2024
Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA.
The treatment of cancers with immunotherapies has yielded significant milestones in recent years. Amongst these immunotherapeutic strategies, the FDA has approved several checkpoint inhibitors (CPIs), primarily Anti-Programmed Death-1 (PD-1) and Programmed Death Ligand-1/2 (PDL-1/2) monoclonal antibodies, in the treatment of various cancers unresponsive to immune therapeutics. Such treatments resulted in significant clinical responses and the prolongation of survival in a subset of patients.
View Article and Find Full Text PDFIn Vivo
December 2024
Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.;
Background/aim: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, though rare, is the most common form of autoimmune encephalitis, predominantly affecting young individuals, particularly females. Standard treatments include corticosteroids, intravenous immunoglobulins (IVIG), and plasmapheresis, with rituximab recommended for those unresponsive to first-line therapies. However, reliable biomarkers for clinical assessment remain elusive.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
D.O.P.O. Clinic, Department of Pediatric Hematology and Oncology, IRCCS Giannina Gaslini Institute, 16147 Genoa, Italy.
Immune dysregulation in Inborn Errors of Immunity (IEI) shows a broad phenotype, including autoimmune disorders, benign lymphoproliferation, and malignancies, driven by an increasing number of implicated genes. Recent findings suggest that childhood cancer survivors (CCSs) may exhibit immunological abnormalities potentially linked to an underlying IEI, along with a well-known increased risk of subsequent malignancies due to prior cancer treatments. We describe a patient with two composite heterozygous pathogenic variants in the interleukin-2-inducible T-cell kinase () gene and a history of multiple tumors, including recurrent Epstein-Barr virus (EBV)-related nodular sclerosis and Hodgkin's lymphoma (NSHL), associated with unresponsive multiple hand warts, immune thrombocytopenia, and an impaired immunological profile (CD4+ lymphocytopenia, memory B-cell deficiency, reduction in regulatory T-cells, and B-cell- and T-cell-activated profiles).
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