Professor Joanne Lysaght
Professor In, Surgery
Biography
Prof. Joanne Lysaght graduated with B.Sc.(Hons) in Science from Maynooth University with maths and biology. She then went on to complete a PhD in 2005, in the Department of Biochemistry and Immunology in Trinity College Dublin, in the area of Tumour Immunology. Following completion of her PhD, she worked in the Cancer Molecular Diagnostic Laboratory based in St. James's Hospital and then took up a post-doctoral position in the Department of Haematology and Oncology, TCD, where she worked on a novel family of chemotherapeutic drugs for the treatment of childhood leukemias. Prof. Lysaght then moved to the Department of Surgery, TCD/St. James's Hospital where her research focused on the role of the adaptive immune system in the link between obesity and gastrointestinal cancer. In 2011 she Lysaght was appointed Ussher Assistant Professor in Molecular Oncology, in 2015 Assistant Professor, in 2017 Associate Professor and Professor in Cancer Immunology and Immunotherapy in 2023, where she continues her research in cancer immunology and immunotherapy.
Prof. Lysaght's research group focus on a number of different areas around the central theme of cancer immunology and immunotherapy. Currently, a major research focus is investigating the impact and scheduling of chemotherapy and radiotherapy, and targeting immunometabolism to enhance anti-tumour immunity when used in combination with immunotherapies, namely immune checkpoint inhibitors. The majority of research in the cancer immunology and immunotherapy group is focused on upper gastrointestinal cancer, particularly oesophageal cancer but also gastric and pancreatic cancer. Research into how the regulation and trafficking of lymphocytes can be targeted to reduced adipose tissue and liver-associated inflammation is also a research interest within the group. Other areas of interest include identifying novel immunotherapeutic targets in the pre-malignant setting such as Barrett's Oesophagus and pancreatic cysts, which can be used to slow or prevent progression to malignancy. Another research interest is the area of obesity and cancer, and how this impacts anti-tumour immunity. Prof. Lysaght's group also investigates the role of adaptive immunity and obesity in the debilitating cancer-associated wasting disease cachexia and sarcopenia.
Publications and Further Research Outputs
Peer-Reviewed Publications
Moran J, Mylod E, Kane LE, Marion C, Keenan E, Mekhaeil M, Lysaght J, Dev KK, O'Sullivan J, Conroy MJ., Investigating the Effects of Olaparib on the Susceptibility of Glioblastoma Multiforme Tumour Cells to Natural Killer Cell-Mediated Responses, Pharmaceutics, 2023
Davern, M. and Bracken-Clarke, D. and Donlon, N.E. and Sheppard, A.D. and Connell, F.O. and Heeran, A.B. and Majcher, K. and Conroy, M.J. and Mylod, E. and Butler, C. and Donohoe, C. and Donnell, D.O. and Lowery, M. and Bhardwaj, A. and Ravi, N. and Melo, A.A. and Sullivan, J.O. and Reynolds, J.V. and Lysaght, J., Visceral adipose tissue secretome from early and late-stage oesophageal cancer patients differentially affects effector and regulatory T cells, Journal of Cancer Research and Clinical Oncology, 2023
Davern M, Donlon NE, O'Connell F, Gaughan C, O'Donovan C, Habash M, Sheppard AD, MacLean M, Dunne MR, Moore J, Temperley H, Conroy MJ, Butler C, Bhardwaj A, Ravi N, Donohoe CL, Reynolds JV, Lysaght J., Acidosis significantly alters immune checkpoint expression profiles of T cells from oesophageal adenocarcinoma patients, Cancer Immunology Immunotherapy, 2023
Moran B, Davern M, Reynolds JV, Donlon NE, Lysaght J., The impact of histone deacetylase inhibitors on immune cells and implications for cancer therapy, Cancer Letters, 2023
Davern M, Donlon NE, O' Connell F, Sheppard AD, Hayes C, King R, Temperley H, Butler C, Bhardwaj A, Moore J, Bracken-Clarke D, Donohoe C, Ravi N, Reynolds JV, Maher SG, Conroy MJ, Lysaght J., Cooperation between chemotherapy and immune checkpoint blockade to enhance anti-tumour T cell immunity in oesophageal adenocarcinoma, Translational Oncology, 2022
Davern M, Donlon NE, Sheppard AS, Majcher KD, Connell FO, Heeran AB, Grant M, Farrell RA, Hayes C, Bracken-Clarke D, Conroy MJ, Foley E, Toole DO, Bhardwaj A, Ravi N, Reynolds JV, Maher SG, Sullivan JO, Lysaght J., FLOT and CROSS chemotherapy regimens alter the frequency of CD27+ and CD69+ T cells in oesophagogastric adenocarcinomas: implications for combination with immunotherapy, Journal of Cancer Research and Clinical Oncology, 2022
Donlon NE, Davern M, Hayes C, Power R, Sheppard AD, Donohoe CL, Lysaght J, Reynolds JV., The immune response to major gastrointestinal cancer surgery and potential implications for adjuvant immunotherapy, Critical reviews in Oncology and Haematology , 2022
Davern M, O' Brien RM, McGrath J, Donlon NE, Melo AM, Buckley CE, Sheppard AD, Reynolds JV, Lynam-Lennon N, Maher SG, Lysaght J., PD-1 blockade enhances chemotherapy toxicity in oesophageal adenocarcinoma., Scientific Reports, 12, (1), 2022, p3259-
Reynolds JV, Donlon NE, Elliott JA, Moran B, Temperley H, Nugent TS, Davern M, King S, Conroy M, Lysaght J, Ravi N, Ryan C, Finn S, Norris S, Donohoe CL., Incidence and Impact of Non-alcoholic Fatty Liver Disease (NAFLD) in Patients with Adenocarcinoma of the Esophagus Treated with Curative Intent., World Journal of Surgery, 2022
Mylod E, McKenna E, Davern M, Barr MP, Donlon NE, Bibby BAS, Bhardwaj A, Reynolds JV, Lysaght J, Maher SG, Conroy MJ, Investigating the susceptibility of treatment-resistant oesophageal tumours to natural killer cell-mediated responses, Clinical and Experimental Medicine, 2022
Mylod E, Lysaght J, Conroy MJ., Natural killer cell therapy: A new frontier for obesity-associated cancer, Cancer Letters, 2022
Davern M, Fitzgerald MC, Buckley CE, Heeran AB, Donlon NE, McGrath J, O' Connell F, Deshpande MR, Hayes C, MacDonald J, Sheppard AD, Reynolds JV, Maher SG, Lynam-Lennon N, Murphy B, Lysaght J., PD-1 and TIGIT blockade differentially affect tumour cell survival under hypoxia and glucose deprived conditions in oesophageal adenocarcinoma; implications for overcoming resistance to PD-1 blockade in hypoxic tumours., Translational Oncology, 19, 2022
Noel E. Donlon, Maria Davern, Andrew D. Sheppard, Fiona O'Connell, Margaret R. Dunne, Conall Hayes, Eimear Mylod, Sinead Ramjit, Hugo Temperley, Michael Mac Lean, Gillian Cotter, Anshul Bhardwaj, Christine Butler, Melissa J. Conroy, Jacintha O'Sullivan, Narayanasamy Ravi, Claire L. Donohoe, John V. Reynolds and Joanne Lysaght, The Impact of Esophageal Oncological Surgery on Perioperative Immune Function; Implications for Adjuvant Immune Checkpoint Inhibition, Frontiers in Immunology, 2022
Noel Donlon, Maria Davern, Andrew Sheppard, Claire Donohoe, John Reynolds, Joanne Lysaght, Novel methods to enhance anti-tumour immunity in oesophageal adenocarcinoma; hypofractionated radiotherapy may be superior to CROSS regimen chemo-radiation, British Journal of Surgery, Association of Surgeons of Great Britain and Ireland, Annual Congress, Liverpool, 3-5th May 2022, 109, (Supplement_5), 2022
Davern M, Donlon NE, O'Connell F, Gaughan C, O'Donovan C, McGrath J, Sheppard AD, Hayes C, King R, Temperley H, MacLean M, Bulter C, Bhardwaj A, Moore J, Donohoe C, Ravi N, Conroy MJ, Reynolds JV, Lysaght J., Nutrient deprivation and hypoxia alter T cell immune checkpoint expression: potential impact for immunotherapy., Journal of Cancer Research and Clinical Oncology, 2022
Donlon NE, Davern M, O'Connell F, Sheppard A, Heeran A, Bhardwaj A, Butler C, Narayanasamy R, Donohoe C, Phelan JJ, Lynam-Lennon N, Dunne MR, Maher S, O'Sullivan J, Reynolds JV, Lysaght J., Impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma, World Journal of Gastroenterology, 2022
Laura E Kane, Gregory S Mellotte, Rebecca G Lyons, Eimear Mylod, Simone Marcone, Paul F Ridway, Finbar MacCarthy, Kevin C Conlon, Joanne Lysaght, Barbara M Ryan, Stephen G Maher, Establishment of a novel multi-omic biomarker panel in cyst fluid and blood for stratifying patient risk of pancreatic cancer, Cancer Research, The American Association for Cancer Research, New Orleans, April 8-13, 82, (12_Supplement), 2022, pp3381 - 3381
Naimimohasses S, O'Gorman P, Wright C, Ni Fhloinn D, Holden D, Conlon N, Monaghan A, Kennedy M, Gormley J, Beddy P, Finn SP, Lysaght J, O'Sullivan J, Dunne MR, Norris S, Moore JB., Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD, Nutrients, 14, (11), 2022, p2198
Donlon, N; Sheppard, A; Davern, M; Donohoe, C; Ravi, N; Reynolds, J; Lysaght, J; , THE EFFECT OF IONISING-RADIATION AND THE TUMOUR MICRO-ENVIRONMENT (TME) ON TREATMENT NAIVE ESOPHAGEAL ADENOCARCINOMA PATIENT T CELL FUNCTION AND ACTIVITY., 2021
Ashanty M.Melo, Eimear Mylod, Vivienne Fitzgerald, Noel E.Donlon, Dearbhla M. Murphy, Emma K.Foley, Anshul Bhardwaj, John V.Reynolds, Derek G.Doherty, Joanne Lysaght, Margaret R. Dunne, Melissa J. Conroy, Tissue distribution of γδ T cell subsets in oesophageal adenocarcinoma, Clinical Immunology, 229, 2021
Mylod E, Melo AM, Donlon NE, Davern M, Bhardwaj A, Reynolds JV, Lysaght J, Conroy MJ., Fractalkine Elicits Chemotactic, Phenotypic, and Functional Effects on CX3CR1+CD27- NK Cells in Obesity-Associated Cancer., Journal of immunology (Baltimore, Md. : 1950), 207, (4), 2021, p1200-1210
O'Donovan C, Davern M, Donlon NE, Lysaght J, Conroy MJ., Chemokine-targeted therapies: An opportunity to remodel immune profiles in gastro-oesophageal tumours., Cancer letters, 521, 2021, p224-236
O'Brien RM, Cannon A, Reynolds JV, Lysaght J, Lynam-Lennon N., Complement in Tumourigenesis and the Response to Cancer Therapy., Cancers, 13, (6), 2021
Conroy MJ, Kennedy SA, Doyle SL, Hayes B, Kavanagh M, van der Stok EP, O'Sullivan K, Cathcart MC, Reynolds JV, Lysaght J., A study of the immune infiltrate and patient outcomes in esophageal cancer., Carcinogenesis, 42, (3), 2021, p395-404
Lorton, Cliona M., Higgins, Larissa, O'Donoghue, Niamh, Donohoe, Claire, O'Connell, Jim, Mockler, David, Reynolds, John V., Walsh, Declan, Lysaght, Joanne, C-Reactive Protein and C-Reactive Protein-Based Scores to Predict Survival in Esophageal and Junctional Adenocarcinoma: Systematic Review and Meta-Analysis, Annals of Surgical Oncology, 2021
Donlon, Noel; Davern, Maria; Sheppard, Andrew; Reynolds, John; Lysaght, Joanne; , From bench to bedside; A rationale for Immunotherapy in the adjuvant setting for Oesophageal cancer, Association of Surgeons of Great Britain and Ireland , 2021
Noel E Donlon, Maria Davern, Andrew Sheppard, Robert Power, Fiona O'Connell, Aisling B Heeran, Ross King, Conall Hayes, Anshul Bhardwaj, James J Phelan, Margaret R Dunne, Narayanasamy Ravi, Claire L Donohoe, Jacintha O'Sullivan, John V Reynolds, Joanne Lysaght., The Prognostic Value of the Lymph Node in Oesophageal Adenocarcinoma; Incorporating Clinicopathological and Immunological Profiling, Cancers, 2021
Donlon, N.E. and Power, R. and Hayes, C. and Davern, M. and Reynolds, J.V. and Lysaght, J., Radiation and immunotherapy in upper gastrointestinal cancers: The current state of play, International Journal of Molecular Sciences, 22, (3), 2021, p1-15
Davern M, Donlon NE, Sheppard A, Connell FO, Hayes C, Bhardwaj A, Foley E, Toole DO, Lynam-Lennon N, Ravi N, Reynolds JV, Maher SG, Lysaght J., Chemotherapy regimens induce inhibitory immune checkpoint protein expression on stem-like and senescent-like oesophageal adenocarcinoma cells., Translational oncology, 14, (6), 2021, p101062
Eimear Mylod , Fiona O'Connell, Noel E. Donlon , Christine Butler , John V. Reynolds, Joanne Lysaght and Melissa J. Conroy, The Omentum in Obesity-Associated Cancer: A Hindrance to Effective Natural Killer Cell Migration towards Tumour Which Can Be Overcome by CX3CR1 Antagonism, Cancers, 14, (64), 2021
Donlon, N.E. and Power, R. and Hayes, C. and Reynolds, J.V. and Lysaght, J., Radiotherapy, immunotherapy, and the tumour microenvironment: Turning an immunosuppressive milieu into a therapeutic opportunity, Cancer Letters, 502, 2021, p84-96
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
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
Royds J, Cassidy H, Conroy M, Dune M.R, Lysaght J, McCrory C, Examination and characterisation of the effect of amitriptyline therapy for chronic neuropathic pain on neuropeptide and proteomic constituents of human cerebrospinal fluid, Brain, Behaviour & Immunity, 2020
Davern, M. and Lysaght, J., Cooperation between chemotherapy and immunotherapy in gastroesophageal cancers, Cancer Letters, 495, 2020, p89-99
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
Donlon, N; Davern, M; Sheppard, A; Elliott, J; Ravi, N; Donohoe, C; Reynolds, J; Lysaght, J; , ENHANCING RADIATION-INDUCED IMMUNOGENICITY IN THE MULTIMODAL TREATMENT OF ESOPHAGEAL CANCER: IS HYPOFRACTIONATION THE ANSWER?, 2020
Melo AM, Maher SG, O'Leary SM, Doherty DG, Lysaght J, Selective effects of radiotherapy on viability and function of invariant natural killer T cells in vitro, Radiotherapy and Oncology, 145, 2020, p128 - 136
CX3CL1 Signaling in the Tumor Microenvironment in, 2020, pp1 - 12, [Conroy, M.J. and Lysaght, J.]
Immunometabolism and Its Potential to Improve the Current Limitations of Immunotherapy in, Methods in Molecular Biology, 2020, pp233-263 , [Sheppard, A.D. and Lysaght, J.]
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
Melo A.M., Conroy M.J., Foley E.K., Dockry E., Breen E.P., Reynolds J.V., Lysaght J., Doherty D.G., CD1d expression and invariant natural killer T-cell numbers are reduced in patients with upper gastrointestinal cancers and are further impaired by commonly used chemotherapies, Cancer Immunology, Immunotherapy, 69, (6), 2020, p969 - 982, p969-982
Cancers: Immunotherapeutic Targets for Gastrointestinal Cancers, MDPI, [eds.], 2020-2022
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
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
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
Cannon, A. and Clarke, N. and MacCarthy, F. and Dunne, C. and Kevans, D. and Mahmud, N. and Lysaght, J. and O'Sullivan, J., Effect of cigarette smoke extract on the intestinal microenvironment of ulcerative colitis tissue, JGH Open, 4, (6), 2020, p1191-1198
Hannon, G. and Lysaght, J. and Liptrott, N.J. and Prina-Mello, A., Immunotoxicity Considerations for Next Generation Cancer Nanomedicines, Advanced Science, (1900133), 2019
Lysaght J., The 'obesity paradox' in action with cancer immunotherapy., Nature reviews. Endocrinology, 15, (3), 2019, p132-133
MÌnch, N.S. and Fang, H.-Y. and Ingermann, J. and Maurer, H.C. and Anand, A. and Kellner, V. and Sahm, V. and Wiethaler, M. and Baumeister, T. and Wein, F. and EinwÀchter, H. and Bolze, F. and Klingenspor, M. and Haller, D. and Kavanagh, M. and Lysaght, J. and Friedman, R. and Dannenberg, A.J. and Pollak, M. and Holt, P.R. and Muthupalani, S. and Fox, J.G. and Whary, M.T. and Lee, Y. and Ren, T.Y. and Elliot, R. and Fitzgerald, R. and Steiger, K. and Schmid, R.M. and Wang, T.C. and Quante, M., High-Fat Diet Accelerates Carcinogenesis in a Mouse Model of Barrett's Esophagus via Interleukin 8 and Alterations to the Gut Microbiome, Gastroenterology, 157, (2), 2019, p492-506.e2
Mongan AM, Lynam-Lennon N, Doyle SL, Casey R, Carr E, Cannon A, Conroy MJ, Pidgeon GP, Brennan L, Lysaght J, Reynolds JV, O'Sullivan J., Visceral Adipose Tissue Modulates Radiosensitivity in Oesophageal Adenocarcinoma., International journal of medical sciences, 16, (4), 2019, p519-528
Lewis, D.E. and Lysaght, J. and Wu, H., Editorial: T cell alterations in adipose tissue during obesity, HIV, and cancer, Frontiers in Immunology, 10, (MAY), 2019
Joanne Lysaght, The 'obesity paradox' in action with cancer immunotherapy, Nature Reviews Endocrinology, 2019
Kavanagh, M.E. and Conroy, M.J. and Clarke, N.E. and Gilmartin, N.T. and Feighery, R. and MacCarthy, F. and Oâ Toole, D. and Ravi, N. and Reynolds, J.V. and Oâ Sullivan, J. and Lysaght, J., Altered T Cell Migratory Capacity in the Progression from Barrett Oesophagus to Oesophageal Adenocarcinoma, Cancer Microenvironment, 2019
Frontiers in Immunology: Editorial: T Cell Alterations in Adipose Tissue During Obesity, HIV, and Cancer, Frontiers, [eds.], 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
Conroy MJ, Maher SG, Melo AM, Doyle SL, Foley E, Reynolds JV, Long A, Lysaght J., Identifying a Novel Role for Fractalkine (CX3CL1) in Memory CD8+ T Cell Accumulation in the Omentum of Obesity-Associated Cancer Patients., Frontiers in immunology, 9, 2018, p1867
Oâ Sullivan, J. and Lysaght, J. and Donohoe, C.L. and Reynolds, J.V., Obesity and gastrointestinal cancer: the interrelationship of adipose and tumour microenvironments, Nature Reviews Gastroenterology and Hepatology, 15, (11), 2018, p699-714
Oâ sullivan, K.E. and Michielsen, A.J. and Oâ regan, E. and Cathcart, M.C. and Moore, G. and Breen, E. and Segurado, R. and Reynolds, J.V. and Lysaght, J. and Oâ sullivan, J., pSTAT3 levels have divergent expression patterns and associations with survival in squamous cell carcinoma and adenocarcinoma of the oesophagus, International Journal of Molecular Sciences, 19, (6), 2018, p1720-
Das, B. and Conroy, M. and Moore, D. and Lysaght, J. and McCrory, C., Human dorsal root ganglion pulsed radiofrequency treatment modulates cerebrospinal fluid lymphocytes and neuroinflammatory markers in chronic radicular pain, Brain, Behavior, and Immunity, 70, 2018, p157-165
Melo, A.M. and Zhang, L. and Dockry, E.F. and Petrasca, A. and Ghnewa, Y.G. and Breen, E.P. and Morrissey, M.E. and O'Reilly, C. and Bruen, R. and O'Meara, A. and Lysaght, J. and Zhu, X. and Doherty, D.G., Novel thioglycoside analogs of α-galactosylceramide stimulate cytotoxicity and preferential Th1 cytokine production by human invariant natural killer T cells, Glycobiology, 28, (7), 2018, p512-521
Donohoe C.L, Lysaght J, O'Sullivan J, Reynolds J.V, Emerging Concepts Linking Obesity with the Hallmarks of Cancer, Trends in Endocrinology and Metabolism, 28, (1), 2017, p46 - 62
Doyle SL, Mongan AM, Donohoe CL, Pidgeon GP, Sherlock M, Reynolds JV, Lysaght J., Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma., Diseases of the Esophagus, 30, (6), 2017, p1 - 11
Conroy M.J, Fitzgerald V, Doyle S.L, Channon S, Useckaite Z, Gilmartin N, Oâ Farrelly C, Ravi N, Reynolds J.V, Lysaght J, The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function, Journal of Leukocyte Biology, 100, (6), 2016, p1435 - 1442
Conroy M.J, Galvin K.C, Doyle S.L, Kavanagh M.E, Mongan A.-M, Cannon A, Moore G.Y, Reynolds J.V, Lysaght J, Parallel Profiles of Inflammatory and Effector Memory T Cells in Visceral Fat and Liver of Obesity-Associated Cancer Patients, Inflammation, 39, (5), 2016, p1729 - 1736
Conroy M.J, Galvin K.C, Kavanagh M.E, Mongan A.M, Doyle S.L, Gilmartin N, O'Farrelly C, Reynolds J.V, Lysaght J, CCR1 antagonism attenuates T cell trafficking to omentum and liver in obesity-associated cancer, Immunology and Cell Biology, 94, (6), 2016, p531 - 537
Kavanagh ME, Conroy MJ, Clarke NE, Gilmartin NT, O'Sullivan KE, Feighery R, MacCarthy F, O'Toole D, Ravi N, Reynolds JV, O'Sullivan J, Lysaght J, Impact of the inflammatory microenvironment on T-cell phenotype in the progression from reflux oesophagitis to Barrett oesophagus and oesophageal adenocarcinoma., Cancer letters, 370, (1), 2016, p117-24
Cathcart M.-C, Useckaite Z, Drakeford C, Semik V, Lysaght J, Gately K, O'Byrne K.J, Pidgeon G.P, Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo, BMC Cancer, 16, (1), 2016, p707-
Kavanagh, M.E., O'Sullivan, K.E., O'Hanlon, C., (...), Lysaght, J., Reynolds, J.V., The esophagitis to adenocarcinoma sequence; the role of inflammation, Cancer Letters, 345, (2), 2014, p182-189
Lynam-Lennon N, Connaughton R, Carr E, Mongan AM, O'Farrell NJ, Porter RK, Brennan L, Pidgeon GP, Lysaght J, Reynolds JV, O'Sullivan J., Excess visceral adiposity induces alterations in mitochondrial function and energy metabolism in esophageal adenocarcinoma., BMC Cancer, 3, (14), 2014, p907-
O'Sullivan KE, Phelan JJ, O'Hanlon C, Lysaght J, O'Sullivan JN, Reynolds JV., The role of inflammation in cancer of the esophagus., Expert Reviews Gastroenterology Hepatology, 8, (7), 2014, p749 - 760
O'Sullivan KE, Reynolds JV, O'Hanlon C, O'Sullivan JN, Lysaght J, Could signal transducer and activator of transcription 3 be a therapeutic target in obesity-related gastrointestinal malignancy?, Journal of gastrointestinal cancer, 45, (1), 2014, p1-11
Ahearne M, Lysaght J, Lynch AP, Combined influence of basal media and fibroblast growth factor on the expansion and differentiation capabilities of adipose-derived stem cells., Cell regeneration (London, England), 3, (1), 2014, p13 - 13
Mockler MB, Conroy MJ, Lysaght J, Targeting T cell immunometabolism for cancer immunotherapy; understanding the impact of the tumor microenvironment., Frontiers in oncology, 4, 2014, p107
Doyle SL, Bennett AM, Donohoe CL, Mongan AM, Howard JM, Lithander FE, Pidgeon GP, Reynolds JV, Lysaght J, Establishing computed tomography-defined visceral fat area thresholds for use in obesity-related cancer research., Nutrition research (New York, N.Y.), 33, (3), 2013, p171-9
Allott EH, Lysaght J, Cathcart MC, Donohoe CL, Cummins R, McGarrigle SA, Kay E, Reynolds JV, Pidgeon GP, MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation., Molecular carcinogenesis, 52, (2), 2013, p144-54
Lysaght J, Verma NK, Maginn EN, Ryan JM, Campiani G, Zisterer DM, Williams DC, Browne PV, Lawler MP, McElligott AM, The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells., International journal of oncology, 42, (1), 2013, p239-46
Donohoe CL, Doyle SL, McGarrigle S, Cathcart MC, Daly E, O'Grady A, Lysaght J, Pidgeon GP, Reynolds JV., Role of the insulin-like growth factor 1 axis and visceral adiposity in oesophageal adenocarcinoma, British Journal of Surgery, 99, (3), 2012, p387-96
Allott EH, Oliver E, Lysaght J, Gray SG, Reynolds JV, Roche HM, Pidgeon GP, The SGBS cell strain as a model for the in vitro study of obesity and cancer., Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 14, (10), 2012, p774-82
Allott EH, Morine MJ, Lysaght J, McGarrigle SA, Donohoe CL, Reynolds JV, Roche HM, Pidgeon GP, Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis., Clinical and translational gastroenterology, 3, 2012, pe12
SL Doyle, C Donohoe, S Finn, J Howard, FE Lithander, JV Reynolds, G Pidgeon, J Lysaght , IGF-1 and its Receptor in Esophageal Cancer: Association with Adenocarcinoma and Visceral Obesity, American Journal of Gastroenterology, 107, 2012, p196 - 204
Doyle SL, Donohoe CL, Lysaght J, Reynolds JV, Viseral obesity, metabolic syndrome, insulin resistance and cancer, Proceedings of the Nutrition Society, 71, (1), 2012, p181-9
Allott EH, Morine MJ, Lysaght J, McGarrigle SA, Donohoe CL, Reynolds JV, Roche HM, Pidgeon GP, Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis, Clinical and Translational Gastroenterology, 3, 2012
Doyle, S.L. and Donohoe, C.L. and Lysaght, J. and Reynolds, J.V., Visceral obesity, metabolic syndrome, insulin resistance and cancer, Proceedings of the Nutrition Society, 71, (1), 2012, p181-189
Cathcart MC, Lysaght J, Pidgeon GP, Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention., Cancer metastasis reviews, 30, (3-4), 2011, p363-85
Carroll PA, Healy L, Lysaght J, Boyle T, Reynolds JV, Kennedy MJ, Pidgeon G, Connolly EM., Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer., Molecular Carcinogenesis, 50, (8), 2011, p643 - 651
J. Lysaght, E.P. van der Stok, E.H. Allott, R. Casey, C.L. Donohoe, J.M. Howard, S.A. McGarrigle, N. Ravi, J.V. Reynolds, G.P. Pidgeon, Pro-inflammatory and tumour proliferative properties of excess visceral adipose tissue, Cancer Letters, 312, (1), 2011, p62-72
Lysaght J, Allott EH, Donohoe CL, Howard JM, Pidgeon GP, Reynolds JV., T lymphocyte activation in visceral adipose tissue of patients with oesophageal adenocarcinoma., British Journal of Surgery, 98, (7), 2011, p964 - 974
Doyle SL, Lysaght J, Reynolds JV, Obesity and post-operative complications in patients undergoing non-bariatric surgery., Obesity reviews : an official journal of the International Association for the Study of Obesity, 11, (12), 2010, p875-86
Donohoe CL, Pidgeon GP, Lysaght J, Reynolds JV., Obesity and gastrointestinal cancer, British Journal of Surgery, 2010
Lynam-Lennon N, Reynolds JV, Pidgeon GP, Lysaght J, Marignol L, Maher SG, Alterations in DNA repair efficiency are involved in the radioresistance of esophageal adenocarcinoma., Radiation research, 174, (6), 2010, p703 - 711
Pidgeon GP, Lysaght J, Krishnamoorthy S, Reynolds JV, O'Byrne K, Nie D, Honn KV., Lipoxygenase metabolism: roles in tumor progression and survival., Cancer Metastasis Reviews, 3-4, 2007, p503 - 524
Lysaght, J., Jarnicki, A. and Mills, K.H.G. , Reciprocal effects of Th1 and Treg cell inducing pathogen-associated immunomodulatory molecules on anti-tumour immunity. , Cancer Immunology and Immunotherapy, Published online Feb, (DOI 10.1007/s00262-0), 2007, p1367 - 1379
Jarnicki, A.G., Lysaght, J, Todryk, S, Mills, K.H.G, Suppression of antitumor immunity by IL-10 and TGF-b-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells., Journal of Immunology, 177, (2), 2006, p896-904
Casey DG, Lysaght J, James T, Bateman A, Melcher AA, Todryk SM., Heat shock protein derived from a non-autologous tumour can be used as an anti-tumour vaccine., Immunology, 110, (1), 2003, p105-11
Lysaght J, Todryk S., Developments in cancer vaccination, Curr Opin Investig Drugs. , 2003
Non-Peer-Reviewed Publications
Cliona M Lorton, Larissa Higgins, Niamh O'Donoghue, Claire Donohoe, Jim O'Connell, David Mockler, John V Reynolds, Declan Walsh, Joanne Lysaght, ASO Visual Abstract: C-Reactive Protein and C-Reactive Protein-Based Scores to Predict Survival in Esophageal and Junctional Adenocarcinoma: Systematic Review and Meta-analysis, Annals of Surgical Oncology, 2021
Cliona M Lorton, John V Reynolds, Joanne Lysaght, ASO Author Reflections: Can CRP and CRP-Based Scores Predict Survival in Operable Adenocarcinomas of the Esophagus and Esophago-Gastric Junction?, Annals of Surgical Oncology, 2021
Research Expertise
Description
My translational research group focuses on the central theme of cancer immunology and immunotherapy, an area that continues to revolutionise treatment for cancer patients worldwide. Cancer immunotherapy has offered cures and extended the lives of countless cancer patients, where no options existed before, but this field is still in its relative infancy. The majority of research in my group is focused on dismal upper gastrointestinal cancers, particularly obesity-associated oesophageal cancer but also gastric, pancreatic and ovarian cancer. A key research direction of my research is understanding how the physical features of the tumour microenvironment, immunometabolism and the cancer treatment itself can affect immune cells, namely T cells, and their functions in cancer patients. This work has been reported in 85 peer-reviewed publications in international journals. Understanding the hurdles faced by T cells in cancer patients will lead to identification of novel and more effective treatment combinations, including immune checkpoint inhibitors with chemotherapy and radiotherapy. It will help identify biomarkers of response and treatment resistance which can be used in the clinical management of these patients. Research into the regulation and chemotaxis (movement) of lymphocytes to reduce pathological inflammation and enhance anti-tumour immunity is another important research theme within my group. My group utilize a range of in vitro and ex vivo molecular and cellular analytical techniques and I have established productive multi-disciplinary collaborations with academic, clinical and industrial partners, both nationally and internationally. To conduct my research, I have received funding from Science Foundation Ireland, Health Research Board, the Irish Cancer Society, Breakthrough Cancer Research and the Irish Research Council.Projects
- Title
- Investigating the immunomodulatory properties of adipose tissue in oesophageal and colorectal cancer.
- Summary
- Obesity has increased markedly over the past two decades and is predicted to overtake smoking as the leading contributing factor for cancer by 2015. The aim of this research project is to study an adipose tissue bioresource from patients undergoing resective surgery for oesophageal and colorectal cancer, to investigate the mechanisms where obesity may contribute to the development and progression of these malignancies. Visceral abdominal fat has been identified as the essential fat depot for patho-genetic theories that relate obesity, metabolic syndrome and cancer. In a prospective study, subpopulations of immune cells in freshly digested, resected peripheral and omental adipose tissue will be characterised. Data will analysed comparing obese and non-obese patients, and patients with or without cancer. Immune cell population will also be assessed in the blood to determine how excess adipose tissue may regulate systemic immune responses, potentially effecting cancers at distal sites. In a retrospective study, the activation status and localisation of distinct immune cells within the tumour microenvironment will be determined by immunohistochemistry using specifically generated tissue micro-arrays. This data will be correlated with clinical parameters including BMI, visceral adiposity, metabolic syndrome status, pathological features and overall survival in order to examine the anti-tumour immune response in obese patients. The ability of adipocytes to act as antigen presenting cells and direct innate and adaptive immune responses will also be examined. This could have important implications in the role of adipose tissue in host defence, immune mediated diseases and cancer. On completion of this project it is anticipated that our knowledge of the regulatory mechanisms linking obesity, metabolic syndrome, immunomodulation and tumour growth will be greatly enhanced, which could identify novel therapeutic targets for the treatment of obesity related cancers.
- Funding Agency
- Health Reseach Board
- Date From
- 2009
- Date To
- 2012
- Title
- Investigating the role of T cells in adipose tissue and hepatic inflammation in obesity associated cancer.
- Summary
- Visceral obesity is considered to be a state of chronic systemic low grade inflammation, driven largely by the release of inflammatory mediators from infiltrating immune cells. Steatohepatitis, is a hepatic inflammatory consequence of visceral adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD). Recent murine studies have demonstrated that excess fat can exacerbate T cell mediated liver injury, by polarising T helper cells towards a Th-1 response. Obesity is also known to enhance lymphocyte responsiveness to hepatic chemokines, resulting in increased lymphocyte trafficking to the liver in response to inflammatory insults. However the characterisation and source of these lymphocytes in humans has not been addressed. Oesophageal adenocarcinoma (OAC) has the fastest growing incidence of all cancers, particularly in Ireland. It has the strongest association with obesity of all cancers and arises in a background of chronic inflammation making it an ideal model to study the role of T cells in adipose tissue and liver inflammation. This novel project will examine the chemoattractant properties of the human omentum and liver in attracting naive or activated T cells in OAC patients. The inflammatory profile in blood, omentum, liver and tumour will be assessed and correlated with visceral obesity. We have previously shown that large populations of activated inflammatory T cells reside within the omentum and this project aims to examine the clonality of these T cells by TCR repertoire restriction analysis and compare it to that of hepatic T cells in matched patients, where they may play a role in NAFLD. Overall this project, the first of its kind, will delineate the role of omental and hepatic T cells in maintaining chronic inflammation in obese cancer patients and potentially identify immunotherapeutic cellular or protein targets in order to control pathological inflammation and enhance anti-tumour immune responses in these patients.
- Funding Agency
- Health Research Board
- Date From
- 2011
- Title
- Evaluating the role of T cells in the progression of Barrett's Oesophagus to Oesophageal Adenocarcinoma: identification of novel immunotherpeutic targets
- Summary
- Barrett's oesophagus (BO) is the pre-malignant link in the progression from reflux oesophagitis to oesophageal adenocarcinoma (OAC), a cancer whose incidence rates are rising rapidly in Ireland. Premalignant conditions that develop in the presence of chronic inflammation are often associated with a dysregulated immune response. The role of T cells in the progression to oesophageal adenocarcinoma is largely unknown, however recent studies suggest that T cells may play a key role in the driving and maintaining inflammation in the oesophagus. This unique study will examine the infiltration and activation of T cells in normal, oesophagitis, BO, dysplastic and OAC tissue using ex-vivo samples. A number of studies have suggested that the local immune microenvironment undergoes a radical change with the progression to adenocarcinoma, starting with an inflammatory cell-mediated like response in oesophagitis, switching to a humoral response in BO and back to an inflammatory response with the emergence of cancer. Therefore, the influence of the local microenvironment on T cell function at each disease stage will be assessed using a variety of T cell functional assays including proliferation, cytokine profiling, cytotoxicity and migration. Tissue conditioned media (TCM), generated by culturing fresh tissue biopsies representative of each disease stage, will be screened by magnetic resonance spectroscopy (NMR) to identify factors capable of regulating T cell phenotype and activation. We hypothesise that specific factors released from the oesophageal tissue as it progresses through the malignant sequence will significantly alter T cell function and ultimately accelerate disease progression. Overall this project, the first of its kind, will identify and functional validate mediators which may act as potential novel immunotherapeutic cellular or protein targets, capable of enhancing the anti-tumour immune response or prevent the progression to adenocarcinoma in these patients.
- Funding Agency
- Health Research Board
- Date From
- 1.10.12
- Date To
- 31.9.15
- Title
- Immunophenotyping of pancreatic cystic lesions
- Funding Agency
- Trinity College Dublin
- Date From
- 2021
- Date To
- 2025
- Title
- Elucidating the role of the Fractalkine pathway in NK cell migration to the adipose tissue in obese cancer patients
- Funding Agency
- Breakthrough Cancer Research
- Title
- Enhancing anti-tumour immunity in Oesophageal cancer through the modulation of immunometabolism with the novel small molecule inhibitor Quininib and its analogues
- Funding Agency
- Irish Research Council
- Date From
- 2018
- Date To
- 2022
- Title
- Investigation of the role of the complement cascade in the radioresistance of rectal cancer
- Funding Agency
- Irish Cancer Society
- Date From
- 2018
- Date To
- 2021
- Title
- Elucidating the pathological role of obesity, inflammation and immunity in cancer related sarcopenia in upper gastrointestinal cancers.
- Funding Agency
- Health Research Board
- Date From
- 2018
- Date To
- 2022
- Title
- Assessment of the predictive value of immune and histological parameters in oesophageal adenocarcinoma using digital pathology.
- Funding Agency
- Health Research Board
- Title
- Prospective validation of the complement system as a novel treatment stratification tool in oesophageal adenocarcinoma patients
- Funding Agency
- Health Research Board
- Title
- Investigating the applicability of novel cancer immunotherapies in upper gastrointestinal cancers and the impact of concurrent combination chemotherapy
- Funding Agency
- Irish Research Council
- Title
- Examination of the therapeutic potential of MK-3475 in the obesity-associated upper gastrointestinal cancer, EAC
- Funding Agency
- Merck Sharpe and Dohme
Recognition
Representations
Irish representative (As President of the Irish Society for Immunology) at the second European Federation of Immunological societies (EFIS) Strategic Planning Meeting in Italy, November 2022. EFIS governs a number of taskforces and research groups, which help generate policies for European Governments on immunological issues such as vaccinations and Covid.
Awards and Honours
Award for Excellence in Supervision of Research Students-School of Medicine Main Award
CROSS Research Fellowship
HRB Post-Doctoral Fellowship
Memberships
President of the Irish Society for Immunology
Senior Council Member of the Irish Association for Cancer Research
European Association for Cancer Research
European Federation of Immunological Societies
International Union of Immunological Societies
Cancer Trials Ireland
Society for Immunotherapy of Cancer (SITC)