Dendritic cells from mesothelioma patients are numerically and functionally impaired

Abstract

Event Abstract Back to Event Dendritic cells from mesothelioma patients are numerically and functionally impaired Scott M. Cornwall1, 2*, Matthew Wikstrom3, Anna Nowak3, John Alvarez3 and Delia J. Nelson1, 2 1 Curtin University, School of Biomedical Sciences, Australia 2 Curtin Health Innovation Research Institute, Australia 3 University of Western Australia, Australia Malignant mesothelioma is an aggressive tumour affecting the mesothelium surrounding the pleura. Diagnosis occurs at a late stage of disease progression with death within twelve months. Current treatment options include surgery, chemotherapy and/or radiotherapy, however, no patients are cured and improved treatment strategies are needed. One possibility is immunotherapy. Dendritic cells (DC) are involved in inducing and maintaining adaptive immunity. Many immunotherapies target DCs yet their functional status in mesothelioma patients is unknown. Therefore, blood DC subsets from mesothelioma patients (n=48) and healthy age-matched controls (n=40) were analysed by flow cytometry. Mesothelioma patients had significantly lower CD303+plasmacytoid (p)DC, CD1c+myeloid (m)DC1 and CD141+mDC2 numbers relative to controls. GM-CSF/IL-4-exposed monocytes from mesothelioma patients differentiated into monocyte-derived DCs (MoDCs) that expressed significantly lower levels of CD40, with decreased trends in CD11c/CD80/CD83/CD86 and HLA-DR expression compared with healthy-derived MoDCs. Mesothelioma-derived MoDCs demonstrated a significantly decreased capacity to process antigen. Stimulation with LPS+/-IFNγ induced incomplete maturation indicated by slight loss of antigen processing ability with limited upregulation of the maturation marker, CD83, and costimulatory molecules CD40/CD80 and CD86. Attempts to rescue DC function through CD40L stimulation did not fully restore CD1a/CD40/CD83/CD86 and HLA-DR expression and antigen processing function remained intact. Nonetheless, MoDCs from mesothelioma patients maintained their ability to induce allogeneic T cell proliferation. Our data suggests that mesothelioma patients have significant numerical and functional defects in their DC subsets and rescue with CD40L offers limited benefit. Furthermore, reduced capacity to process antigen and reduced costimulatory molecules suggests that T cells will be anergized/tolerized. Keywords: Dendritic Cells, Cancer, Humans, Mesothelioma, immune dysfunction Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Cornwall SM, Wikstrom M, Nowak A, Alvarez J and Nelson DJ (2013). Dendritic cells from mesothelioma patients are numerically and functionally impaired. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01019 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Mr. Scott M Cornwall, Curtin University, School of Biomedical Sciences, Perth, Western Australia, 6102, Australia, scott.cornwall@postgrad.curtin.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Scott M Cornwall Matthew Wikstrom Anna Nowak John Alvarez Delia J Nelson Google Scott M Cornwall Matthew Wikstrom Anna Nowak John Alvarez Delia J Nelson Google Scholar Scott M Cornwall Matthew Wikstrom Anna Nowak John Alvarez Delia J Nelson PubMed Scott M Cornwall Matthew Wikstrom Anna Nowak John Alvarez Delia J Nelson Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.