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Identification of a gene score related to antigen processing and presentation machinery for predicting prognosis in head and neck squamous cell carcinoma and its potential implications for immunotherapy.
Clin Transl Oncol
December 2024
Department of Otolaryngology, Research Units of New Technologies of Endoscopic Surgery in Skull Base Tumor (2018RU003), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100000, China.
Background: Despite its crucial role in immune surveillance and cell survival of tumors, the significance of MHC antigen processing and presentation machinery (APM) is still not fully understood in head and neck squamous cell carcinoma (HNSCC). We sought to develop an APM gene score (APMGS) to predict prognosis and reveal the molecular and immune traits of the APMGS-defined subgroups in HNSCC.
Methods: Based on the APM-related genes acquired from 6 databases, 117 combined machine learning algorithms were applied to develop APMGS with The Cancer Genome Atlas (TCGA)-HNSCC database and validated with the Gene Expression Omnibus (GEO) dataset.
Regulation of the cell surface expression of classical and non-classical MHC proteins by the human cytomegalovirus UL40 and rhesus cytomegalovirus Rh67 proteins.
J Virol
September 2024
Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Unlabelled: The signal sequences of the human cytomegalovirus (CMV) UL40 protein and its rhesus CMV (RhCMV) counterpart, Rh67, contain a peptide (VMAPRT[L/V][F/I/L/V]L, VL9) that is presented by major histocompatibility complex (MHC) antigen E (MHC-E). The CMV VL9 peptides replace VL9 peptides derived from classical MHC (Ia) signal sequences, which are lost when CMV disrupts antigen processing and presentation and MHC Ia expression. This allows infected cells to maintain MHC-E surface expression and escape killing by Natural Killer cells.
View Article and Find Full Text PDFA luminescence-based method to assess antigen presentation and antigen-specific T cell responses for screening of immunomodulatory checkpoints and therapeutics.
Front Immunol
August 2023
Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Investigations into the strength of antigen-specific responses is becoming increasingly relevant for decision making in early-phase research of novel immunotherapeutic approaches, including adoptive cell but also immune checkpoint inhibitor (ICI)-based therapies. In the latter, antigen-specific rapid and high throughput tools to investigate MHC/antigen-specific T cell receptor (TCR) activation haven't been implemented yet. Here, we present a simple and rapid luminescence-based approach using the human papillomavirus 16 (HPV16) E7 peptide as model antigen and E7-TCR transgenic Jurkat.
View Article and Find Full Text PDFInterferons and Resistance Mechanisms in Tumors and Pathogen-Driven Diseases-Focus on the Major Histocompatibility Complex (MHC) Antigen Processing Pathway.
Int J Mol Sci
April 2023
Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112 Halle, Germany.
Interferons (IFNs), divided into type I, type II, and type III IFNs represent proteins that are secreted from cells in response to various stimuli and provide important information for understanding the evolution, structure, and function of the immune system, as well as the signaling pathways of other cytokines and their receptors. They exert comparable, but also distinct physiologic and pathophysiologic activities accompanied by pleiotropic effects, such as the modulation of host responses against bacterial and viral infections, tumor surveillance, innate and adaptive immune responses. IFNs were the first cytokines used for the treatment of tumor patients including hairy leukemia, renal cell carcinoma, and melanoma.
View Article and Find Full Text PDFIonizing Radiation Drives Key Regulators of Antigen Presentation and a Global Expansion of the Immunopeptidome.
Mol Cell Proteomics
November 2022
Oxford Cancer Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; The Jenner Institute, University of Oxford, Oxford, United Kingdom. Electronic address:
Little is known about the pathways regulating MHC antigen presentation and the identity of treatment-specific T cell antigens induced by ionizing radiation. For this reason, we investigated the radiation-specific changes in the colorectal tumor cell proteome. We found an increase in DDX58 and ZBP1 protein expression, two nucleic acid sensing molecules likely involved in induction of the dominant interferon response signature observed after genotoxic insult.
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