Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope Presentation in Diffuse Large B Cell Lymphoma Patients

Improved therapies are urgently needed for patients with diffuse large B cell lymphoma (DLBCL). Success using immune checkpoint inhibitors and chimeric antigen receptor T cell technology has fuelled demand for validated cancer epitopes. Immunogenic cancer testis antigens (CTAs), with their widesprea...

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Main Authors: Kamel Ait-Tahar, Amanda P. Anderson, Martin Barnardo, Graham P. Collins, Chris S. R. Hatton, Alison H. Banham, Karen Pulford
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Advances in Hematology
Online Access:http://dx.doi.org/10.1155/2017/6527306
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author Kamel Ait-Tahar
Amanda P. Anderson
Martin Barnardo
Graham P. Collins
Chris S. R. Hatton
Alison H. Banham
Karen Pulford
author_facet Kamel Ait-Tahar
Amanda P. Anderson
Martin Barnardo
Graham P. Collins
Chris S. R. Hatton
Alison H. Banham
Karen Pulford
author_sort Kamel Ait-Tahar
collection DOAJ
description Improved therapies are urgently needed for patients with diffuse large B cell lymphoma (DLBCL). Success using immune checkpoint inhibitors and chimeric antigen receptor T cell technology has fuelled demand for validated cancer epitopes. Immunogenic cancer testis antigens (CTAs), with their widespread expression in many tumours but highly restricted normal tissue distribution, represent attractive immunotherapeutic targets that may improve treatment options for DLBCL and other malignancies. Sperm protein 17 (Sp17), a CTA reported to be immunogenic in ovarian cancer and myeloma patients, is expressed in DLBCL. The aim of the present study was to investigate Sp17 epitope presentation via the presence of a cytotoxic T cell (CTL) and a CD4 T-helper (Th) response in DLBCL patients. A significant γ-interferon CTL response was detected in peripheral blood mononuclear cells of 13/31 DLBCL patients following short-term cell stimulation with two novel HLA-A⁎0201 peptides and one previously reported HLA-A⁎0101-restricted nine-mer Sp17 peptide. No significant responses were detected in the HLA-A⁎0201-negative DLBCL patients or four healthy subjects. A novel immunogenic 20-mer CD4 Th Sp17 peptide was detected in 8/17 DLBCL patients. This is the first report of a CTL and a CD4 Th response to Sp17 in DLBCL and supports Sp17 as a potential immunotherapeutic target for DLBCL.
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spelling doaj-art-d51b6cff87684ef0aa59f3727a1873ee2025-02-03T00:59:01ZengWileyAdvances in Hematology1687-91041687-91122017-01-01201710.1155/2017/65273066527306Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope Presentation in Diffuse Large B Cell Lymphoma PatientsKamel Ait-Tahar0Amanda P. Anderson1Martin Barnardo2Graham P. Collins3Chris S. R. Hatton4Alison H. Banham5Karen Pulford6Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UKNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UKTransplant Immunology & Immunogenetics, Oxford Transplant Centre, Churchill Hospital, Oxford, UKDepartment of Clinical Haematology, Churchill Hospital, Oxford, UKDepartment of Clinical Haematology, Churchill Hospital, Oxford, UKNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UKNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UKImproved therapies are urgently needed for patients with diffuse large B cell lymphoma (DLBCL). Success using immune checkpoint inhibitors and chimeric antigen receptor T cell technology has fuelled demand for validated cancer epitopes. Immunogenic cancer testis antigens (CTAs), with their widespread expression in many tumours but highly restricted normal tissue distribution, represent attractive immunotherapeutic targets that may improve treatment options for DLBCL and other malignancies. Sperm protein 17 (Sp17), a CTA reported to be immunogenic in ovarian cancer and myeloma patients, is expressed in DLBCL. The aim of the present study was to investigate Sp17 epitope presentation via the presence of a cytotoxic T cell (CTL) and a CD4 T-helper (Th) response in DLBCL patients. A significant γ-interferon CTL response was detected in peripheral blood mononuclear cells of 13/31 DLBCL patients following short-term cell stimulation with two novel HLA-A⁎0201 peptides and one previously reported HLA-A⁎0101-restricted nine-mer Sp17 peptide. No significant responses were detected in the HLA-A⁎0201-negative DLBCL patients or four healthy subjects. A novel immunogenic 20-mer CD4 Th Sp17 peptide was detected in 8/17 DLBCL patients. This is the first report of a CTL and a CD4 Th response to Sp17 in DLBCL and supports Sp17 as a potential immunotherapeutic target for DLBCL.http://dx.doi.org/10.1155/2017/6527306
spellingShingle Kamel Ait-Tahar
Amanda P. Anderson
Martin Barnardo
Graham P. Collins
Chris S. R. Hatton
Alison H. Banham
Karen Pulford
Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope Presentation in Diffuse Large B Cell Lymphoma Patients
Advances in Hematology
title Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope Presentation in Diffuse Large B Cell Lymphoma Patients
title_full Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope Presentation in Diffuse Large B Cell Lymphoma Patients
title_fullStr Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope Presentation in Diffuse Large B Cell Lymphoma Patients
title_full_unstemmed Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope Presentation in Diffuse Large B Cell Lymphoma Patients
title_short Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope Presentation in Diffuse Large B Cell Lymphoma Patients
title_sort sp17 protein expression and major histocompatibility class i and ii epitope presentation in diffuse large b cell lymphoma patients
url http://dx.doi.org/10.1155/2017/6527306
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