Publications and Further Research Outputs
Peer-Reviewed Publications
Aisling B. Heeran, Margaret R. Dunne, Maria E. Morrissey, Croí E. Buckley, Niamh Clarke, Aoife Cannon, Noel E. Donlon, Timothy S. Nugent, Michael Durand, Cara Dunne, John O. Larkin, Brian Mehigan, Paul McCormick, Niamh Lynam-Lennon, Jacintha O"Sullivan, The Protein Secretome Is Altered in Rectal Cancer Tissue Compared to Normal Rectal Tissue, and Alterations in the Secretome Induce Enhanced Innate Immune Responses, Cancers, 13, (3), 2021, p571
Davern M, Donlon NE, Power R, Hayes C, King R, Dunne MR, Reynolds JV., The tumour immune microenvironment in oesophageal cancer., British journal of cancer, 2021
Kennedy, S.A., Annett, S.L., Dunne, M.R., Boland, F., O'Neill, L.M., Guinan, E.M., Doyle, S.L., Foley, E.K., Elliott, J.A., Murphy, C.F., Bennett, A.E., Carey, M., Hillary, D., Robson, T., Reynolds, J.V., Hussey, J., O'Sullivan, J.N., Effect of the Rehabilitation Program, ReStOre, on Serum Biomarkers in a Randomized Control Trial of Esophagogastric Cancer Survivors, Frontiers in Oncology, 11, (669078), 2021, p1-11
Orumaa K, Dunne MR., The role of unconventional T cells in COVID-19., Ir J Med Sci, 2021
King R, Hayes C, Donohoe CL, Dunne MR, Davern M, Donlon NE., Hypoxia and its impact on the tumour microenvironment of gastroesophageal cancers., World journal of gastrointestinal oncology, 13, (5), 2021, p312-331
Dunne MR, Wagener J, Loeffler J, Doherty DG, Rogers TR, Unconventional T cells - New players in antifungal immunity, Clinical Immunology, 2021, p108734-
Power R, Lowery MA, Reynolds JV, Dunne MR., The Cancer-Immune Set Point in Oesophageal Cancer., Frontiers in oncology, 10, 2020, p891
Noel E. Donlon and Andrew Sheppard and Maria Davern and Fiona O'Connell and James J. Phelan and Robert Power and Timothy Nugent and Kate Dinneen and John Aird and John Greene and Paul Nevins Selvadurai and Anshul Bhardwaj and Emma K. Foley and Narayanasamy Ravi and Claire L. Donohoe and John V. Reynolds and Joanne Lysaght and Jacintha O'Sullivan and Margaret R. Dunne, Linking Circulating Serum Proteins with Clinical Outcomes in Esophageal Adenocarcinoma"An Emerging Role for Chemokines, Cancers, 12, (11), 2020, p3356
Moore D, Galvin D, Conroy MJ, Das B, Dunne M, Lysaght J, McCrory C., Characterisation of the effects of pulsed radio frequency treatment of the dorsal root ganglion on cerebrospinal fluid cellular and peptide constituents in patients with chronic radicular pain: A randomised, triple-blinded, controlled trial., Journal of neuroimmunology, 343, 2020, p577219
Royds J, Cassidy H, Conroy MJ, Dunne MR, Matallanas D, Lysaght J, McCrory C., An Investigation into Proteomic Constituents of Cerebrospinal Fluid in Patients with Chronic Peripheral Neuropathic Pain Medicated with Opioids- a Pilot Study., Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2020
Royds J, Conroy MJ, Dunne MR, McCrory C, Lysaght J., An investigation into the modulation of Tcell phenotypes by amitriptyline and nortriptyline, European Neuropsychopharmacology, 2020
Dunne M.R.*, Phelan J.J.*, Michielsen A.J., Maguire A.A., Dunne C., Martin P., Noonan S., Tosetto M., Geraghty R., Fennelly D., Sheahan K., Ryan E.J., O'Sullivan J. (joint 1st author *), Characterising the prognostic potential of HLA-DR during colorectal cancer development., Cancer Immunology Immunotherapy, 2020
Dunne MR, Byrne G, Chirdo FG, Feighery C., Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder., Frontiers in immunology, 11, 2020, p1374
Susan A. Kennedy and Maria E. Morrissey and Margaret R. Dunne and Fiona O'Connell and Clare T. Butler and Mary-Clare Cathcart and Amy M. Buckley and Brian J. Mehigan and John O. Larkin and Paul McCormick and Breand{\'{a, Combining 1,4-dihydroxy quininib with Bevacizumab/FOLFOX alters angiogenic and inflammatory secretions in ex vivo colorectal tumors, BMC Cancer, 20, (1), 2020
Royds J, Conroy MJ, Dunne MR, Cassidy H, Matallanas D, Lysaght J, McCrory C., Examination and characterisation of burst spinal cord stimulation on cerebrospinal fluid cellular and protein constituents in patient responders with chronic neuropathic pain - A Pilot Study., Journal of neuroimmunology, 344, 2020, p577249
Morrissey ME, Byrne R, Nulty C, McCabe NH, Lynam-Lennon N, Butler CT, Kennedy S, O'Toole D, Larkin J, McCormick P, Mehigan B, Cathcart MC, Lysaght J, Reynolds JV, Ryan EJ, Dunne MR, O'Sullivan J., The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation., BMC Cancer, 20, (1), 2020, p566
Pisarska MM, Dunne MR, O'Shea D, Hogan AE., Interleukin-17 producing mucosal associated invariant T cells - emerging players in chronic inflammatory diseases?, European journal of immunology, 50, (8), 2020, p1098-1108
Buckley AM, Dunne MR, Morrissey ME, Kennedy SA, Nolan A, Davern M, Foley EK, Clarke N, Lysaght J, Ravi N, O'Toole D, MacCarthy F, Reynolds JV, Kennedy BN, O'Sullivan J., Real-time metabolic profiling of oesophageal tumours reveals an altered metabolic phenotype to different oxygen tensions and to treatment with Pyrazinib., Scientific reports, 10, (1), 2020, p12105
Melo, Ashanty M., O'Brien, Aisling M., Phelan, James J., Kennedy, Susan A., Wood, Nicole A. W., Veerapen, Natacha, Besra, Gurdyal S., Clarke, Niamh E., Foley, Emma K., Ravi, Akshaya, MacCarthy, Finbar, O'Toole, Dermot, Ravi, Narayamasami, Reynolds, John V., Conroy, Melissa J., Hogan, Andrew E., O'Sullivan, Jacintha, Dunne, Margaret R., Mucosal-Associated Invariant T Cells Display Diminished Effector Capacity in Oesophageal Adenocarcinoma, Frontiers in Immunology, 10, 2019
Fromm S, Cunningham CC, Dunne MR, Veale DJ, Fearon U, Wade SM., Enhanced angiogenic function in response to fibroblasts from psoriatic arthritis synovium compared to rheumatoid arthritis., Arthritis research & therapy, 21, (1), 2019, p297
Amy Buckley, Becky Bibby, Margaret Dunne, Susan Kennedy, Maria Davern, Breandan Kennedy, Stephen Maher, Jacintha O'Sullivan, Characterisation of an isogenic model of cisplatin resistance in oesophageal adenocarcinoma cells, Pharmaceuticals, 2019
Buckley AM, Dunne MR, Lynam-Lennon N, Kennedy SA, Cannon A, Reynolds AL, Maher SG, Reynolds JV, Kennedy BN, O'Sullivan J., Pyrazinib (P3), [(E)-2-(2-Pyrazin-2-yl-vinyl)-phenol], a small molecule pyrazine compound enhances radiosensitivity in oesophageal adenocarcinoma., Cancer letters, 447, 2019, p115-129
Dunne PJ, Maher CO, Freeley M, Dunne K, Petrasca A, Orikiiriza J, Dunne MR, Reidy D, O'Dea S, Loy A, Woo J, Long A, Rogers TR, Mulcahy F, Doherty DG, CD3" Expression Defines Functionally Distinct Subsets of V"1 T Cells in Patients With Human Immunodeficiency Virus Infection., Frontiers in Immunology, 2018
*Galvin KC, *Conroy MJ, Doyle SL, Dunne MR, Fahey R, Foley E, O'Sullivan KE, Doherty DG, Geoghegan JG, Ravi N, O'Farrelly C, Reynolds JV, Lysaght J., Extratumoral PD-1 blockade does not perpetuate obesity-associated inflammation in esophageal adenocarcinoma., Cancer Letters, 418, 2018, p230-238
Buckley AM, Lynam-Lennon N, Kennedy SA, Dunne MR, Aird JJ, Foley EK, Clarke N, Ravi N, O'Toole D, Reynolds JV, Kennedy BN, O'Sullivan J., Leukaemia inhibitory factor is associated with treatment resistance in oesophageal adenocarcinoma., Oncotarget, 9, (72), 2018, p33634-33647
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
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
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
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]
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
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]
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
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
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
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
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
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
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
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 focused on elucidating the function of innate lymphocytes, in particular γδ T cells and dendritic cells and their contribution to host immunity in diseases such as coeliac disease and cancer. My current work involves investigating the prognostic potential of immune markers in oesophageal cancer.Projects
- Title
- Promoting Education and Research Knowledge (PERK)
- Summary
- THE PROBLEM Cancer of the oesophagus (food pipe) is an aggressive type of cancer, and has a low survival rate. It is usually diagnosed at a late stage, often due to a lack of knowledge of underlying symptoms which can be mild, including heartburn, bloating and problems swallowing. Oesophageal cancer is not as well known as some other cancers since it occurs less often. However, cases are expected to double in Ireland within the next 20 years, so there is an urgent need to improve public knowledge of oesophageal cancer. OUR PROJECT Our project aims to develop communication tools for the public to learn more about oesophageal cancer, and how they can become actively involved in cancer research. We will work with patients and the public to create educational materials including a website, posters, pamphlets, and public information seminars to highlight current cutting-edge research in oesophageal cancer ongoing at St James's Hospital. The website and public events will allow people to directly contact us, so they can ask questions, give feedback on studies, or volunteer to be involved in the design of our future research programme. SUMMARY Our overall goal is to improve public awareness and encourage early detection of oesophageal cancer, by providing a plaform for the public to interact with our research team. This project will allow the public to learn about, have a say in, and become more actively involved in cancer research, and allow us to develop a more patient-centred approach to our future research.
- Funding Agency
- Health Research Board
- Date From
- 1st Dec 2018
- Date To
- 30th Nov 2019
- Title
- Assessment of the predictive value of immune and histological parameters in oesophageal adenocarcinoma using digital pathology
- Summary
- The goal of this study is to determine whether various tumour-scoring methods can predict patient clinical outcomes in OAC, such as response to neo-CRT treatment. Oesophageal adenocarcinoma (OAC) is an aggressive cancer with a five-year survival of <15%, and incidence is predicted to double in Ireland within the next 20 years. Current neo-adjuvant chemotherapy or chemoradiotherapy (neo-CRT) treatment strategies only benefit a minority (20-30% of patients) and there are currently no methods available to differentiate between responders and nonresponders. Therefore, the majority of OAC patients given neo-CRT therapy will experience unnecessary side-effects and delays in time to surgery. The Immunoscore method involves measurement of immune markers (CD3, CD8, and CD45RO) in tumours and has shown superior predictive value to current UICC/TNM staging systems in colorectal cancer. We intend to assess the prognostic value of the traditional Immunoscore in OAC, and also in combination with expression of another immune marker, HLA-DR, which we have previously shown to have significant prognostic potential. Other tumour characteristics such as tumour budding, poorly differentiated clusters, percentage tumour stroma and lymphovascular invasion and density, which have shown promise as prognostic markers in other cancer types, will also be assessed in the novel context of OAC, for their ability to predict patient outcomes. Digital pathology methodology will be employed to standardise our measurements and minimise variability. Circulating markers of inflammation will also be measured in matched OAC patient serum, and levels will be correlated with tumour microenvironment scores. We aim to develop standardised methods of reliably measuring tumour and immune characteristics of potential prognostic value in OAC, which may be adopted for routine use in hospitals. As well as its timely clinical relevance, this project will yield plentiful data on the role of the immune system in cancer, and the factors required for successful tumour eradication.
- Funding Agency
- Health Research Board
- Date From
- 01-12-2017
- Date To
- 01-06-2020
- 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
Recognition
Representations
Presented a poster at the European Congress for Immunology, Amsterdam
Presented a poster at the 2017 Cell Symposium in San Diego, USA.
Presented a poster at the CRUK's Oesophageal Symposium, Cambridge, UK.
Poster presentation at the 9th International Cancer Conference, Trinity Biomedical Sciences Institute, Dublin
Oral presentation at the 8th National Barrett's Symposium, University College London
Presented 2 posters at the Irish Association for Cancer Research annual meeting, Galway
Oral presentations at the Irish Society for Immunology annual meeting
Poster presentation at the 5th International γδ T cell conference, Freiburg, Germany
Oral presentation at the 25th Working Group on Prolamin Analysis & Toxicity (WGPAT), Fellbach, Germany
Poster presentation at the 14th International Coeliac Disease Symposium, Oslo, Norway
Poster presentation at Trinity College Dublin Tercentenary Symposium, Dublin
Poster presentation at 4th International γδ T cell conference, Kiel, Germany
Poster presentation at Institute of Molecular Medicine annual conference, Dublin
Poster presentations at Irish Society for Immunology annual meetings
Awards and Honours
Health Research Award
Irish Research Council Government of Ireland Postdoctoral Fellow
Dorothy Price medal (NUI Maynooth)
John & Pat Hume Postgraduate Scholarship
Irish Research Council for Science, Engineering & Technology Postgraduate Scholarship
Memberships
Member of the Irish Society for Immunology
Member of the Irish and European Associations for Cancer Research (IACR, EACR)
Member of the γδ T cell forum