Radiation Response in Oesophageal Cancer: the role of visceral fat tissue in controlling response through immune-metabolic regulation

Fiona O’Connell

Oesophageal cancer is cancer of the oesophagus, the pipe connecting the mouth to the stomach, is an aggressive disease, the occurrence of which is expected to double in the next twenty years with increasing obesity rates in Ireland and worldwide.

Oesophageal cancer is the cancer that is most highly associated with obesity. This project is focused on finding out the link between obesity and oesophageal cancer and it’s response to radiation therapy. The aim of Fiona’s project is to look at how obesity effects the response of the immune system by looking at how adipose (fat) tissue taken from obese and non-obese patients effects how different cells from the immune system grow and work.

Her project will then look at whether healthy dietary fats effect how the immune system responds to radiation treatment and if these fats could be used to change how the immune system responds to radiation treatment.

At the end of this project, a profile should be developed that shows a different signature for patients that will respond to radiation therapy and those that won’t respond to radiation therapy as well as how obesity will affect the response to radiation. This is a patient-focused project aims to have a significant impact on Oesophageal cancer patient response to treatment prior to surgery. Our findings will allow better understanding of events controlling treatment response and resistance in oesophageal cancer patients.

Publications

10.3390/cancers15061681 Cancers 2023, 15

Mylod E, O’Connell F, Donlon NE, Butler C, Reynolds JV, Lysaght J, and Conroy MJ. The Omentum in Obesity-Associated Cancer: A Hindrance to Effective Natural Killer Cell Migration towards Tumour Which Can Be Overcome by CX3CR1 Antagonism. Cancers 2022, 14(1), 64; https://doi.org/10.3390/cancers14010064

O’Connell F, O’Sullivan J. Help or hindrance: The obesity paradox in cancer treatment response. Cancer Lett. 2021 Dec 1;522:269-280. doi: 10.1016/j.canlet.2021.09.021. Epub 2021 Sep 15. PMID: 34534616. https://pubmed.ncbi.nlm.nih.gov/34534616/

Essa N, O’Connell F, Prina-Mello A, O’Sullivan J, Marcone S. Gold nanoparticles and obese adipose tissue microenvironment in cancer treatment. Cancer Lett. 2021 Oct 15:S0304-3835(21)00528-0. doi: 10.1016/j.canlet.2021.10.017. Epub ahead of print. PMID: 34662546. https://pubmed.ncbi.nlm.nih.gov/34662546/

Donlon NE, Davern M, Sheppard A, Power R, O’Connell F, Heeran AB, King R, Hayes C, Bhardwaj A, Phelan JJ, Dunne MR, Ravi N, Donohoe CL, O’Sullivan J, Reynolds JV, Lysaght J. The Prognostic Value of the Lymph Node in Oesophageal Adenocarcinoma; Incorporating Clinicopathological and Immunological Profiling. Cancers (Basel). 2021 Aug 9;13(16):4005. doi: 10.3390/cancers13164005. PMID: 34439160; PMCID: PMC8391676. https://pubmed.ncbi.nlm.nih.gov/34439160/

Susan A Kennedy, Maria E Morrissey, Margaret R Dunne, Fiona O’Connell, Clare T Butler, Mary-Clare Cathcart, Amy M Buckley, Brian J Mehigan, John O Larkin , Paul McCormick , Breandán N Kennedy , Jacintha O’Sullivan^. Combining 1,4-dihydroxy quininib with Bevacizumab/FOLFOX alters angiogenic and inflammatory secretions in ex vivo colorectal tumors. BMC Cancer. 2020 Oct 2;20(1):952. doi: 10.1186/s12885-020-07430-y

Kayleigh Slater, Aisling B Heeran, Sandra Garcia-Mulero, Helen Kalirai, Rebeca Sanz-Pamplona, Arman Rahman, Nebras Al-Attar, Mays Helmi, Fiona O’Connell, Rosa Bosch, Anna Portela, Alberto Villanueva, William M Gallagher, Lasse D Jensen, Josep M Piulats, Sarah E Coupland, Jacintha O’Sullivan, Breandán N Kennedy High Cysteinyl Leukotriene Receptor 1 Expression Correlates with Poor Survival of Uveal Melanoma Patients and Cognate Antagonist Drugs Modulate the Growth, Cancer Secretome, and Metabolism of Uveal Melanoma Cells.  Cancers (Basel) 2020 Oct 13;12(10):2950. doi: 10.3390/cancers12102950