Harnessing the power of the immune system to fight obesity associated cancer

Eimear Mylod

Obesity is a growing health problem around the world and can cause many diseases. Obese people are at higher risk of cancers such as oesophageal cancer which is a cancer of the food-pipe. Today, most people with oesophageal cancer don’t respond to available treatment options, meaning survival rates are low. The immune system is essential for fighting cancer, but it is often faulty in cancer patients. Treatments that aim to use the immune system to help fight cancer are called immunotherapies. In recent years immunotherapy has been heralded as a major breakthrough for cancer treatment.

Natural killer cells are the body’s own first-line defence against cancer and are important for cancer-killing. This team has shown that these important cancer-killing natural killer cells are pulled into the fat in oesophageal cancer patients, where they die. This reduces the body’s ability to fight cancer. The movement of immune cells, including natural killer cells, around the body, is controlled by molecules called chemokines. They have shown that chemokines are dysregulated in oesophageal cancer and are guiding immune cells to the fat instead of cancer.

Eimear’s research study will test whether targeting chemokines can redirect natural killer cell movement towards the tumour in oesophageal cancer patients. They hope that this offers the therapeutic potential to boost natural killer cell movement to the site of cancer and help to eliminate it.

Publications

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 202214(1), 64; https://doi.org/10.3390/cancers14010064

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. J Immunol. 2021 Aug 15;207(4):1200-1210. doi: 10.4049/jimmunol.2000987. Epub 2021 Jul 28. PMID: 34321227.
Melo AM, Mylod E, Fitzgerald V, Donlon NE, Murphy DM, Foley EK, Bhardwaj A, Reynolds JV, Doherty DG, Lysaght J, Dunne MR, Conroy MJ. Tissue distribution of γδ T cell subsets in oesophageal adenocarcinoma. Clin Immunol. 2021 Aug;229:108797. doi: 10.1016/j.clim.2021.108797. Epub 2021 Jul 15. PMID: 34273585.

 

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Start year:
2019
Principal Investigators:
Dr Melissa Conroy & Associate Professor Joanne Lysaght
Researcher
Eimear Mylod
Host Institution:
Trinity College Dublin
Cancer type:
Oesophageal
Linked Breakthrough Research Priorities: 
1, 2, 4

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