Chee J, Young A, Lesterhuis WJ, Thomas HE.
Funding: US Department of Defense Career Development Award, Mesothelioma Applied Research Foundation
Synopsis: Malignant mesothelioma is an aggressive and incurable cancer caused by asbestos. Immunotherapy is an exciting option for mesothelioma treatment, because it can lead to long-term tumor 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 tumor shrinkage and side effects. However, we do not understand how immune cells behave in tumors and organs after immunotherapy, and if they attack tumor or organ cells in the same manner. Therefore there are no strategies to prevent immune cells from causing side effects, whilst preserving the anti-tumor immune response.
This project aims to compare attacking immune cells in organs versus tumors 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 tumor. As it is unethical to surgically remove organs from cancer patients, we will conduct our study in tumor bearing animals treated with immunotherapy. We will characterise millions of genes and proteins in individual immune cells from affected organs and tumors, 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-tumor responses. Our project will benefit patients by developing novel strategies to prevent severe immunotherapy related side effects.