Dr Melissa Conroy
People with cancer of the food-pipe (oesophageal cancer (OC)) receive treatments that only work in 30% of patients. Therefore, ~70% of all OC patients will not benefit from chemo-radiotherapy and urgently need new drugs. Our immune system is designed to kill cancer cells, but in cancer patients the immune system is weakened. Natural killer (NK) cells are the cancer-eradicating assassins of the immune system. OC patients who lack NK cells have worst outcomes and poorest response to chemo-radiotherapy. We have reported that NK cells in obese OC patients are pulled into the fat by a protein called fractalkine. Once in the fat, NK cells die and therefore never reach or destroy the tumour. Consequently, highest obesity levels are linked to lowest numbers of NK cells in oesophageal tumours.
Weakened immune systems can be overcome by drugs called immunotherapies. We have demonstrated that an immunotherapy called a CX3CR1 antagonist blocks fractalkine from pulling NK cells into the fat. In this study, we will evaluate whether this drug can free NK cells to move towards
and kill oesophageal tumours.
Secondly, we will examine if injection of healthy NK cells can be used
to restore diminished immune cells and boost tumour destruction in OC.
Finally, we will edit this NK cell immunotherapy for obese OC patients to make the NK cells resistant to fractalkine, so they bypass the fat and move towards the oesophageal tumour. Ultimately, we will confirm whether two novel
immunotherapies have potential to improve survival rates for all OC patients.