scholarly journals T Cell-Tumor Interaction Directs the Development of Immunotherapies in Head and Neck Cancer

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
A. E. Albers ◽  
L. Strauss ◽  
T. Liao ◽  
T. K. Hoffmann ◽  
A. M. Kaufmann
Keyword(s):  
T Cell ◽  
Head And Neck ◽  
Antigen Processing ◽  
Cell Tumor ◽  
Tumor Escape ◽  
Effector Cells ◽  
Antitumor Effector ◽  
Tumor Escape Mechanism ◽  
Lymphocyte Homeostasis ◽  
Antigen Processing And Presentation

The competent immune system controls disease effectively due to induction, function, and regulation of effector lymphocytes. Immunosurveillance is exerted mostly by cytotoxic T-lymphocytes (CTLs) while specific immune suppression is associated with tumor malignancy and progression. In squamous cell carcinoma of the head and neck, the presence, activity, but also suppression of tumor-specific CTL have been demonstrated. Functional CTL may exert a selection pressure on the tumor cells that consecutively escape by a combination of molecular and cellular evasion mechanisms. Certain of these mechanisms target antitumor effector cells directly or indirectly by affecting cells that regulate CTL function. This results in the dysfunction or apoptosis of lymphocytes and dysregulated lymphocyte homeostasis. Another important tumor-escape mechanism is to avoid recognition by dysregulation of antigen processing and presentation. Thus, both induction of functional CTL and susceptibility of the tumor and its microenvironment to become T cell targets should be considered in CTL-based immunotherapy.

scholarly journals Antigen processing and presentation in cancer immunotherapy

2020 ◽  
Vol 8 (2) ◽  
pp. e001111 ◽  
Author(s):  
Maxwell Y Lee ◽  
Jun W Jeon ◽  
Cem Sievers ◽  
Clint T Allen
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
In Silico ◽  
Antigen Processing ◽  
Tumor Antigens ◽  
Epitope Prediction ◽  
Cell Tumor ◽  
Class I ◽  
Wide Range ◽  
Antigen Processing And Presentation

BackgroundKnowledge about and identification of T cell tumor antigens may inform the development of T cell receptor-engineered adoptive cell transfer or personalized cancer vaccine immunotherapy. Here, we review antigen processing and presentation and discuss limitations in tumor antigen prediction approaches.MethodsOriginal articles covering antigen processing and presentation, epitope discovery, and in silico T cell epitope prediction were reviewed.ResultsNatural processing and presentation of antigens is a complex process that involves proteasomal proteolysis of parental proteins, transportation of digested peptides into the endoplasmic reticulum, loading of peptides onto major histocompatibility complex (MHC) class I molecules, and shuttling of peptide:MHC complexes to the cell surface. A number of T cell tumor antigens have been experimentally validated in patients with cancer. Assessment of predicted MHC class I binding and total score for these validated T cell antigens demonstrated a wide range of values, with nearly one-third of validated antigens carrying an IC50 of greater than 500 nM.ConclusionsAntigen processing and presentation is a complex, multistep process. In silico epitope prediction techniques can be a useful tool, but comprehensive experimental testing and validation on a patient-by-patient basis may be required to reliably identify T cell tumor antigens.

scholarly journals Transcriptome Profiling of IL-17A Preactivated Mesenchymal Stem Cells: A Comparative Study to Unmodified and IFN-γModified Mesenchymal Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Kisha Nandini Sivanathan ◽  
Darling Rojas-Canales ◽  
Shane T. Grey ◽  
Stan Gronthos ◽  
Patrick T. Coates
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Antigen Processing ◽  
Cellular Therapy ◽  
Human Mesenchymal Stem Cells ◽  
Humoral Response ◽  
Transcriptome Profiling ◽  
Antigen Processing And Presentation ◽  
Immunomodulatory Function

Human mesenchymal stem cells pretreatment with IL-17A (MSC-17) potently enhances T cell immunosuppression but not their immunogenicity, in addition to avidly promoting the induction of suppressive regulatory T cells. The aim of this study was to identify potential mechanisms by which human MSC-17 mediate their superior immunomodulatory function. Untreated-MSC (UT-MSC), IFN-γtreated MSC (MSC-γ), and MSC-17 were assessed for their gene expression profile by microarray. Significantly regulated genes were identified for their biological functions (Database for Annotation, Visualisation and Integrated Discovery, DAVID). Microarray analyses identified 1278 differentially regulated genes between MSC-γand UT-MSC and 67 genes between MSC-17 and UT-MSC. MSC-γwere enriched for genes involved in immune response, antigen processing and presentation, humoral response, and complement activation, consistent with increased MSC-γimmunogenicity. MSC-17 genes were associated with chemotaxis response, which may be involved in T cell recruitment for MSC-17 immunosuppression. MMP1, MMP13, and CXCL6 were highly and specifically expressed in MSC-17, which was further validated by real-time PCR. Thus, MMPs and chemokines may play a key role in mediating MSC-17 superior immunomodulatory function. MSC-17 represent a potential cellular therapy to suppress immunological T cell responses mediated by expression of an array of immunoregulatory molecules.

scholarly journals Uncovering the modified immunopeptidome reveals insights into principles of PTM-driven antigenicity

2021 ◽  
Author(s):  
Assaf Kacen ◽  
Aaron Javitt ◽  
Matthias P Kramer ◽  
David Morgenstern ◽  
Tomer Tsaban ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
Clinical Samples ◽  
Systematic Analysis ◽  
Post Translational Modifications ◽  
Binding Motifs ◽  
Host Interactions ◽  
Modified Peptides ◽  
Specific Antigens ◽  
Antigen Processing And Presentation

Antigen processing and presentation are critical for modulating tumor-host interactions. While post-translational modifications (PTMs) can alter the binding and recognition of antigens, their identification remains challenging. Here we uncover the role PTMs may play in antigen presentation and recognition in human cancers by profiling 29 different PTM combinations in immunopeptidomics data from multiple clinical samples and cell lines. We established and validated an antigen discovery pipeline and showed that newly identified modified antigens from a murine cancer model are cancer-specific and can elicit T cell killing. Systematic analysis of PTMs across multiple cohorts defined new haplotype preferences and binding motifs in association with specific PTM types. By expanding the antigenic landscape with modifications, we uncover disease-specific targets, including thousands of novel cancer-specific antigens and reveal insight into PTM-driven antigenicity. Collectively, our findings highlight an immunomodulatory role for modified peptides presented on HLA I, which may have broad implications for T-cell mediated therapies in cancer and beyond.

Abstract B34: Melanoma cells respond to CD8+ T cell attack by upregulation of genes associated with antigen processing and presentation

2017 ◽  
Author(s):  
Natalie J. Neubert ◽  
Laure Tillé ◽  
David Barras ◽  
Charlotte Soneson ◽  
Petra Baumgaertner ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
Cd8 T Cell ◽  
Melanoma Cells ◽  
Antigen Processing And Presentation

scholarly journals 910 Overexpression of miR-155–5p can upregulate antigen processing and presentation pathway via targeting tapasin

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A956-A956
Author(s):  
Yuan Wang ◽  
Maria-Filothei Lazaridou ◽  
Chiara Massa ◽  
Barbara Seliger
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
In Silico ◽  
Posttranscriptional Regulation ◽  
Antigen Processing ◽  
In Silico Analysis ◽  
Surface Expression ◽  
Class I ◽  
Antigen Processing And Presentation ◽  
Silico Analysis

BackgroundDysregulation of major histocompatibility complex (MHC) class I antigen processing and presentation machinery (APM) components in the tumor as one main molecular mechanism of immune escape leading to deactivation of T cell immune surveillance could be due to post-transcriptional regulation via immune-modulatory microRNAs (miRNA). It is now well established from a variety of studies that several miRNAs could effectively modulate the expression of some MHC class I APM components in tumors. Tapasin is an important APM molecule involved in the association of MHC class I with transporter associated with antigen processing (TAP) and peptide loading. Since so far no detailed investigation of the posttranscriptional regulation of tapasin exists, the aim of this study is to identify and functionally characterize miRNAs targeting tapasin in melanoma.MethodsUsing miRNA trapping by RNA in vitro affinity purification (miTRAP) and in silico as well as small RNA sequencing, miRNAs will be identified, which bind to the 3’untranslated region (3’ UTR) of tapasin. Dual-luciferase assays will be performed to determine to bind of the miRNA. In silico analysis was performed to predict the effect of miRNAs on the survival of melanoma patients in correlation to tapasin. RT-qPCR, Western blot, flow cytometry, and other functional assays were performed after transfecting miRNA mimics in three melanoma cell lines.ResultsUsing the combination strategy of miTRAP and RNA seq we identified miR-155-5p to bind to the 3’UTR of tapasin, which was further confirmed by in silico analysis and dual-luciferase reporter assay. Transfection of miR-155-5p mimics demonstrated that miR-155-5p upregulate tapasin protein level, which was accompanied by an upregulation of the MHC class I (HLA-ABC) surface expression. Simultaneously, in several different types of cancer, including melanoma, the expression of miR-155-5p is significantly positively correlated with the patient‘s survival and HLA-A protein.ConclusionsOur data revealed for the first time a positive role of miR-155-5p in the posttranscriptional regulation of tapasin in melanoma and provide further insights into the miR-155-5p-mediated induction of HLA-ABC surface expression. This might lead to a better T cell response, avoidance tumor cell escape, improvement of patients‘ survival and thus might be a potential therapeutic target.AcknowledgementsThe work was supported by a grant from the DKH (BS).

Sign in / Sign up

Export Citation Format

Share Document