Margaret Dunne
Senior Research Fellow, Surgery

Publications and Further Research Outputs

Peer-Reviewed Publications

Dunne M., Michielsen A., O"Sullivan K., Cathcart M., Feighery R., Doyle B., Doyle B., Watson J., O"Farrell N., Ravi N., Kay E., Reynolds J., Ryan E., O"Sullivan J., HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients, Cancer Immunology, Immunotherapy, 66, (7), 2017, p841-850 Journal Article, 2017 TARA - Full Text DOI

Guinan, E.M., Doyle, S.L., O"Neill, L., Dunne, M.R., Foley, E.K., O"Sullivan, J., Reynolds, J.V., Hussey, J., Effects of a multimodal rehabilitation programme on inflammation and oxidative stress in oesophageal cancer survivors: the ReStOre feasibility study, Supportive Care in Cancer, 25, (3), 2016, p749 - 756 Journal Article, 2016 DOI

Dunne M., Dunne M., Ryan C., Nolan B., Nolan B., Tosetto M., Tosetto M., Geraghty R., Winter D., Winter D., O'Connell P., O'Connell P., Hyland J., Hyland J., Doherty G., Doherty G., Sheahan K., Sheahan K., Sheahan K., Ryan E., Ryan E., Fletcher J., Fletcher J., Enrichment of inflammatory IL-17 and TNF-" secreting CD4+ T cells within colorectal tumors despite the presence of elevated CD39+ T regulatory cells and increased expression of the immune checkpoint molecule, PD-1, Frontiers in Oncology, 6, (MAR), 2016 Journal Article, 2016 TARA - Full Text DOI

Conroy MJ, Dunne MR, Donohoe CL, Reynolds JV, Obesity-associated cancer: an immunological perspective., The Proceedings of the Nutrition Society, 75, (2), 2015, p125 - 138 Journal Article, 2015 DOI

Comerford R, Coates C, Byrne G, Lynch S, Dunne P, Dunne M, Kelly J, Feighery C, Characterisation of tissue transglutaminase-reactive T cells from patients with coeliac disease and healthy controls , Clinical Immunology, 154, (2), 2014, p155 - 163 Journal Article, 2014 URL DOI

Dunne, MR, Elliott, L, Hussey, S, Mahmud, N, Kelly, J, Doherty, DG, Feighery, CF, Persistent Changes in Circulating and Intestinal gamma delta T Cell Subsets, Invariant Natural Killer T Cells and Mucosal-Associated Invariant T Cells in Children and Adults with Coeliac Disease, PLOS ONE, 8, (10), 2013, p76008 Journal Article, 2013 URL TARA - Full Text DOI

Mangan BA, Dunne MR, O'Reilly VP, Dunne PJ, Exley MA, O'Shea D, Scotet E, Hogan AE, Doherty DG, CD1d restriction and Th1/Th2/Th17 cytokine secretion by human Vδ3 T cells, Journal of Immunology, 191, (1), 2013, p30 - 34 Journal Article, 2013 URL DOI TARA - Full Text

O'Shea D, Corrigan M, Dunne MR, Woods C, Gaoatswe G, O'Connell J, Hogan AE, Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection, International Journal of Obesity, 37, (11), 2013 Journal Article, 2013 DOI

Hogan AE, O'Reilly V, Dunne MR, Dere RT, Zeng SG, O'Brien C, Amu S, Fallon PG, Exley MA, O'Farrelly C, Zhu X, Doherty DG, Activation of human invariant natural killer T cells with a thioglycoside analogue of á-galactosylceramide, Clinical Immunology, 140, (2), 2011, p196-207 Journal Article, 2011 TARA - Full Text

Dunne MR, Madrigal-Estebas L, Tobin LM, Doherty DG, (E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate-stimulated Vã9Vä2 T cells possess T helper type 1-promoting adjuvant activity for human monocyte-derived dendritic cells, Cancer Immunology Immunotherapy , 59, 2010, p1109 - 1120 Journal Article, 2010 DOI URL TARA - Full Text

Dunne MR, Mangan BA, Madrigal-Estebas L, Doherty DG, Preferential Th1 Cytokine Profile of Phosphoantigen-Stimulated Human Vγ9Vδ2 T Cells, Mediators of Inflammation, 2010, (704941), 2010 Journal Article, 2010 DOI TARA - Full Text

Non-Peer-Reviewed Publications

Flow Cytometric Analysis of Human Small Intestinal Lymphoid Cells in, editor(s)Anthony W Ryan , Celiac Disease Methods and Protocols, Humana Press, 2015, [Dunne MR] Book Chapter, 2015 DOI

Celiac Disease: Background and Historical Context in, editor(s)Anthony W Ryan , Celiac Disease , Springer, 2015, pp3 - 14, [Graham D. Turner, Margaret R. Dunne, Anthony W. Ryan] Book Chapter, 2015 URL

Research Expertise

Description

My research involves improving the understanding of roles played by innate immune cells in human health and disease, and translation of this information for therapeutic applications. My research projects to date have focussed on elucidating the function of innate lymphocytes, in particular γδ T cells and dendritic cells, in health and disease, and their contribution to host immunity.

Projects

  • Title
    • Development of prognostic screening tools to predict patient response to neoadjuvant chemoradiotherapy treatment for oesophageal adenocarcinoma
  • Summary
    • Oesophageal adenocarcinoma (OAC) is an aggressive malignancy with poor prognosis, and incidence has increased 5-fold in the last 30 years. Multi-modal neoadjuvant chemoradiotherapy (neo-CT) regimens are increasingly adopted with surgery as the standard of care. However, 70-80% of patients do not respond to neo-CT and may suffer unnecessary side effects and delay to surgery. There is currently no way to predict which patients will respond to neo-CT treatment. We aim to develop methods for identifying OAC patients likely to benefit from neo-CT treatment by histological analysis of tumour tissue at the time of diagnosis. We have previously demonstrated a strong correlation between expression of the major histocompatibility complex class II molecule HLA-DR and patient survival. We hypothesise that HLA-DR may also be used to predict patient responses to neo-CT treatment. We are also interested in characterising cells expressing HLA-DR in tumours, in order to gain a better understanding of immune responses in OAC. As well as analysing specific markers, we will also explore the use of prognostic tumour scoring strategies to predict patient responses to neo-CT treatment. Such scoring strategies grade the level of immune response evident in the tumour microenvironment and have been shown to be useful in predicting patient outcomes in colorectal cancer. To date no such application of this technology has been tested in OAC. This work will aid patient stratification, avoiding unnecessary treatment and ultimately improve current treatment strategies.
  • Funding Agency
    • Health Research Board
  • Date From
    • 2nd May 2016
  • Date To
    • 30th April 2019
  • Title
    • Investigating the role of innate lymphocyte subsets in oesophageal adenocarcinoma - is inflammation a negative regulator of response to therapy?
  • Summary
    • Oesophageal adenocarcinoma is an aggressive cancer with poor prognosis, and incidence has increased 5-fold in the last 30 years. Multi-modal neoadjuvant therapy, either chemotherapy alone (neo-CT) or combination chemoradiation (neo-CRT) is increasingly adopted as the standard of care, but standard clinicopathological parameters are unable to predict patient responsiveness to these approaches. Approximately 70-80% of patients are unresponsive and may be harmed by the delay to surgery and unnecessary treatment toxicity. Our group is currently leading an international phase III clinical trial, comparing the efficacy of two neoadjuvant regimens for treatment of oesophageal adenocarcinoma - the MAGIC regimen, (3 pre- and 3 post-operative 3 week cycles of chemotherapy), and the CROSS protocol (5 weekly cycles of chemotherapy and 5 weeks of radiation therapy). During this trial, blood and tissue samples will be available (both pre- and post-neo-CRT treatment) and ethical approval has been granted to conduct research studies. We will use these samples to investigate the role of inflammation in oesophageal adenocarcinoma and in response to therapy. It is widely reported that inflammation drives tumour initiation and progression by promoting proliferation and survival of malignant cells, angiogenesis and metastasis, by subverting adaptive immune responses and by altering responses to hormones and chemotherapeutic agents. However, inflammation is also pre-requisite for the generation of an effective anti-tumour adaptive immune response. Clarification of the modes of action of inflammatory mediators will allow exploration of how the prevailing inflammatory response may be directed in favour of adaptive responses rather than tumour development. We aim to evaluate the inflammatory contributions of unconventional innate lymphocytes, specifically γδ T cells (Vδ1, Vδ2 and Vδ3 subsets) and mucosal associated invariant T (MAIT) cells. Despite considerable interest in these cells as immunotherapeutic agents, little information exists on their role in the oesophagus, let alone their potential as therapeutic targets.
  • Funding Agency
    • Irish Research Council
  • Title
    • Investigating the role of regulatory T cells in colorectal cancer
  • Funding Agency
    • Science Foundation Ireland
  • Date From
    • Oct 2012
  • Date To
    • Sept 2013
  • Title
    • Elucidating the role of innate lymphocytes in coeliac disease pathogenesis
  • Summary
    • Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56(+) T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.
  • Funding Agency
    • Children's Medical Research Foundation
  • Date From
    • March 2010
  • Date To
    • Sept 2012

Keywords

COELIAC DISEASE; COLORECTAL CANCER; HUMAN DENDRITIC CELLS; HUMAN T-CELLS; Mucosal-associated invariant T cells ; OESOPHAGEAL ADENOCARCINOMA; TCR GAMMA DELTA(+) T CELLS

Recognition

Representations

Presented a poster at the 2017 Cell Symposium in San Diego, USA. 12-06-2017

Presented a poster at the CRUK's Oesophageal Symposium, Cambridge, UK. 27/04/2017

Poster presentation at the 9th International Cancer Conference, Trinity Biomedical Sciences Institute, Dublin Sept 2014

Oral presentation at the 8th National Barrett's Symposium, University College London April 2014

Presented 2 posters at the Irish Association for Cancer Research annual meeting, Galway Feb 2014

Oral presentations at the Irish Society for Immunology annual meeting 2013, 2009, 2008 & 2007

Poster presentation at the 5th International γδ T cell conference, Freiburg, Germany 2012

Oral presentation at the 25th Working Group on Prolamin Analysis & Toxicity (WGPAT), Fellbach, Germany 2011

Poster presentation at the 14th International Coeliac Disease Symposium, Oslo, Norway 2011

Poster presentation at Trinity College Dublin Tercentenary Symposium, Dublin 2011

Poster presentation at 4th International γδ T cell conference, Kiel, Germany 2010

Poster presentation at Institute of Molecular Medicine annual conference, Dublin 2008

Poster presentations at Irish Society for Immunology annual meetings 2010 & 2011

Awards and Honours

Health Research Award 02/05/2016

Irish Research Council Government of Ireland Postdoctoral Fellow 2014

Dorothy Price medal (NUI Maynooth) 2008

John & Pat Hume Postgraduate Scholarship 2005

Irish Research Council for Science, Engineering & Technology Postgraduate Scholarship 2005

Memberships

Member of the Irish Society for Immunology 2005 – Present

Member of the Irish and European Associations for Cancer Research (IACR, EACR) 2013 – Present

Member of the γδ T cell forum 2010 – Present