Funding: Mesothelioma Applied Research Foundation
Synopsis: Immunotherapy is an exciting option for mesothelioma treatment, because it can lead to long-term tumour shrinkage in some patients. However, immunotherapy causes side effects, some of which severely affect vital organs such as the liver, heart, lungs, pancreas and guts. The immune system is responsible for both tumour shrinkage and side effects. However, we do not understand how immune cells behave in tumours and organs after immunotherapy, and if they attack tumour or organ cells in the same manner. Therefore there are no strategies to prevent immune cells from causing side effects, whilst preserving the anti-tumour immune response.
This project aims to compare attacking immune cells in organs versus tumours after immunotherapy. We propose that understanding differences in immune cells found at the scene of the crime will help us develop new ways to disarm them in organs but not the tumour. As it is unethical to surgically remove organs from cancer patients, we will conduct our study in tumour bearing animals treated with immunotherapy. We will characterise millions of genes and proteins in individual immune cells from affected organs and tumours, and identify drug targets based on their differences. We will subsequently test these drugs in combination with immunotherapy to determine if they can prevent side effects, whilst preserving robust anti-tumour responses. Our project will benefit patients by developing novel strategies to prevent severe immunotherapy related side effects.