Irish study may lead to new cancer treatments

Focus on oesophageal cancer
  • Deborah Condon

Researchers in Trinity College Dublin (TCD) have made a discovery, which could lead to new treatments for oesophageal cancer.

Cancer of the oesophagus is a very aggressive type of cancer. It has a poor prognosis, with the five-year survival rate typically less than 15%.

As obesity increases the risk, rising obesity rates have led to it becoming one of the fastest growing cancers in the developed world. Incidence of the disease is expected to double in Ireland over the coming decades.

While new treatments targeting the immune system (immunotherapy) have produced excellent results in other types of cancer, the latest clinical trials suggest that these do not benefit the majority of patients with oesophageal cancer. Current treatment strategies only work for around 25% of patients, so new ones are urgently needed.

The TCD researchers have, for the first time with oesophageal cancer, identified the cancer-killing capability of a lesser known type of immune cell.

The cancer immunopathology research team from the Trinity Translational Medicine Institute (TTMI), based in St James's Hospital, are studying unconventional types of immune cells with lesser known functions.

T cells are a type of white blood cell, which play a key role in fighting cancer by preventing tumours arising and killing off established tumours if activated in the correct way.

Until now, the majority of immune-based studies have largely focused on conventional CD8 (cytotoxic) T cells, but unconventional T cells, while less abundant, can also have potent-cancer killing ability.

The researchers investigated a particular type of T cell, known as a MAIT cell (mucosal-associated invariant cell) in oesophageal cancer. MAIT cells are known to protect against bacterial infections, but little is known about their role when it comes to cancer.

The TCD team is the first to report the characterisation of MAIT cells in the oesophageal cancer setting. They looked at MAIT cells blood and tumours from patients with oesophageal cancer or a pre-cancerous disorder called Barrett's oesophagus, and found that:

- MAIT cells are decreased in the blood of cancer patients, compared to healthy donors, but are found in oesophageal tumours at higher levels than healthy tissues
- MAIT cell levels are not affected by chemoradiotherapy treatment, unlike other T cell types
- Healthy MAIT cells can kill oesophageal cancer cells in a test tube, but this killing is reduced when liquid from fresh tumour biopsies is present, meaning that factors from the tumour can prevent MAIT cell killing
- MAIT cells taken from oesophageal tumours showed high levels of markers associated with functional inhibition. This means that oesophageal tumours seem to be able to stop MAIT cells from killing them, by using these inhibitory markers to deliver a ‘do not kill' signal.

The researchers said that overall, these results suggest an anti-tumour function for a new potential therapeutic target cell in this aggressive cancer type, which is being inhibited by the tumour itself. Finding new ways to reverse the inhibition of MAIT cell tumour-killing ability may offer a new therapeutic strategy in the fight against this type of cancer.

"Oesophageal cancer rates are rising in Ireland, and improved treatment strategies are urgently needed. By revealing how lesser studied immune cells work in cancer, we can better understand the shortcomings of current immunotherapies and investigate new ways to boost the anti-cancer immune response," explained Principal Investigator, Dr Margaret Dunne.

She said that while immunotherapies have "revolutionised" cancer treatment, they still only work for an minority of people.

"A more in-depth understanding of underlying biology will be critical to unravel why this is - and to allow more patients to benefit," she added.

Details of these findings are published in the journal, Frontiers in Immunology.


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