Exploring the role of T cells when immunotherapy for melanoma fails

Professor Peter Hersey

Professor Peter Hersey

Centenary InstituteCancer Council NSW Funding: $450,000Funding duration: 2018-2020

Background

Melanoma is the third most common cancer in Australia and it kills around 1700 Australians each year. A leading treatment is immunotherapy, which involves helping the body fight the cancer itself by targeting molecules called ‘immune checkpoints’ on immune cells. Immune checkpoints act like switches that turn off an attack by immune cells on the cancer. When checkpoints are blocked by drugs called inhibitors, the immune response against cancer is boosted, tumours can often shrink and people live longer. But there is a relapse rate of approximately 40 to 60% after two years of this type of drug treatment and the reason for this is not known.

The research

This project is focused on overcoming the problem of relapse of melanoma in patients being treated by immunotherapy with checkpoint inhibitors. It will examine whether the relapse is associated with a change in immune cells referred to as T cell exhaustion and where this change can be reversed by treatment with certain drugs. In viral infections, it is well established that T cells can lose their ability to kill virus infected cells, so it’s thought something similar could be happening with immunotherapy.

The impact

If successful, this project will establish the role of ‘T cell exhaustion’ in treatment failure in melanoma patients being treated with immunotherapy. It has potential to identify treatments which may reverse the exhausted state and restore the tumour-fighting activity of the T cells. Addressing these important scientific questions will pave the way for new drugs that could reduce the relapse rate of patients having this treatment. This would benefit not only patients with melanoma, but also other types of cancer as this type of immunotherapy is being used for an increasing number of cancers, including lung and Hodgkin lymphoma.

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