The application of TCR sequencing to understand how an individual’s immune system contributes to therapy success

Chee J, Nowak A, Lake R, Lesterhuis WJ, Chopra A, Watson M, Holt R, Zaitouny A.

Funding: icare Dust Diseases Board

Synopsis: Immunotherapy targeting checkpoint inhibitors can lead to cures in some cancer patients, and is an exciting treatment that is currently tested in patients with malignant mesothelioma. Immunotherapy works exceptionally well in a minority of cancer patients. As immunotherapy is expensive, and may cause severe side effects, it is important to accurately predict which patients will benefit from therapy. Immunotherapy acts by improving the patient’s immune cells (in particular T cells) to clear tumours. Each patient has a different combination of unique structures on their T cells called antigen receptors. We believe that these unique receptors are a reason why only some patients respond to therapy. We have the technology to study millions of these receptors at the same time, unlocking the code to understand why an individual may benefit from immunotherapy. We will study T cell receptors in patients with mesothelioma, how they change after chemo-immunotherapy, and find out if these changes affect the outcome of therapy. These findings will be important for developing novel predictors that will inform therapy decisions for mesothelioma patients.

NCARD Research Team

Jonathan Chee, Richard Lake, Anna Nowak, Joost Lesterhuis

Students: Nicola Principe (PhD 2019-), Joel Kidman (PhD 2019 – 2023)