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Research Tags

Age related diseases Angiogenesis Biomedical sciences Cancer genetics and cell biology including metastasis cancer immunology Cell and tissue maintenance, repair and ageing Cellular, molecular and developmental immunology Chronic inflamation Coeliac disease COLORECTAL CANCER Diagnostics gastrointestinal cancer Health outcomes HUMAN DENDRITIC CELLS HUMAN T-CELLS immune prognostic markers Immune system Immunoassays In vitro testing, trial methods Innate immunology Leukocyte Biology Medical Sciences, Research Mucosal immunology Mucosal-associated invariant T cells OESOPHAGEAL ADENOCARCINOMA Oesophageal cancer Oesophageal, gastric, intestinal and pancreatic diseases Pathology Predictive Biomarkers Public health TCR GAMMA DELTA(+) T CELLS Tumour immunology and immunotherapy unconventional T cells

Research Projects

Project Title

Promoting Education and Research Knowledge (PERK)

From

1st Dec 2018

30th Nov 2019

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

Programme

Knowledge Exchange and Dissemination Scheme

Project Type

Patient Oriented Research

Person Months

Project Title

Assessment of the predictive value of immune and histological parameters in oesophageal adenocarcinoma using digital pathology

From

01-12-2017

01-06-2020

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

Programme

Investigator Led Programme

Person Months

Project Title

Development of prognostic screening tools to predict patient response to neoadjuvant chemoradiotherapy treatment for oesophageal adenocarcinoma

From

2nd May 2016

30th April 2019

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

Programme

Health Research Award

Project Type

Patient Oriented Research

Person Months

Project Title

Investigating the role of innate lymphocyte subsets in oesophageal adenocarcinoma - is inflammation a negative regulator of response to therapy?

From

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

Programme

Postdoctoral Fellowship

Project Title

Investigating the role of regulatory T cells in colorectal cancer

From

Oct 2012

Sept 2013

Summary

Funding Agency

Science Foundation Ireland

Project Type

Postdoctoral fellowship

Person Months

Page 1 of 2

Representations

Details	Date
Presented a poster at the European Congress for Immunology, Amsterdam	2-5th Sept
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

Languages

Language	Skill Reading	Skill Writing	Skill Speaking
English	Fluent	Fluent	Fluent

Memberships

Membership of Professional Institutions, Associations, Societies

Details	Date From	Date To
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

Publications and other Research Outputs

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 , Journal Article, PUBLISHED

Orumaa K, Dunne MR., The role of unconventional T cells in COVID-19., Ir J Med Sci, 2021, Journal Article, PUBLISHED DOI

Dunne MR, Wagener J, Loeffler J, Doherty DG, Rogers TR, Unconventional T cells - New players in antifungal immunity, Clinical Immunology, 2021, p108734-, Journal Article, PUBLISHED DOI URL

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, Journal Article, PUBLISHED DOI

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 , Journal Article, PUBLISHED DOI

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 , Journal Article, PUBLISHED DOI

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, Journal Article, PUBLISHED DOI URL

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, Journal Article, PUBLISHED

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 , Journal Article, PUBLISHED TARA - Full Text

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, Journal Article, PUBLISHED DOI

Page 1 of 4

Awards and Honours

Award	Date
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

Research Interests

Description Of Research Interests

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.

Trinity College Dublin, The University of Dublin

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Dr. Margaret Dunne

Dr. Margaret Dunne

Visiting Research Fellow (Clinical Medicine)

dunnem12@tcd.ie

Research Tags

Research Projects

Representations

Languages

Memberships

Membership of Professional Institutions, Associations, Societies

Publications and other Research Outputs

Publications

Awards and Honours

Research Interests

Description Of Research Interests