Dr Colm Keane
Career Establishment Grant 2015
Sponsored by Bridgestone Australia Ltd
Recipient: Dr Colm Keane
The University of Queensland Diamantina
Project title: Net
tumoural immunity and its impact on
outcome in lymphoma
Disease focus: Lymphoma
Funding: $50,000 per year for three years
Funding period: 2015-2017
Dr Colm Keane is developing a new prognostic test to predict lymphoma patients who will benefit from a new type of cancer treatment called ‘immune checkpoint therapy’.
Immune checkpoint proteins can stop our white blood cells from fighting against cancer, acting as molecular ‘dimmer switches’ to reduce the body’s immune response. In many cancers, including lymphomas, the immune checkpoint proteins are not functioning normally and the body is unable to destroy cancer cells.
Using human antibodies, it is possible to block immune checkpoint proteins and restore the immune response. Two new classes of immune-checkpoint therapies – anti-PD-1 and anti-CTLA4 – are being used to successfully prolong life in people with metastatic melanoma.
Dr Keane believes immune checkpoint therapies, such as the anti-PD1 antibody, could be used for treating lymphomas.
In previous research he discovered it was possible to predict the survival of patients with diffuse large B-cell lymphoma (DLBCL) – the most common aggressive B-cell lymphoma – by measuring the ratio of the protein CD8 to the immune checkpoint protein CD163.
Higher levels of CD8 indicated a high number of T-cells. A higher ratio of CD8 to CD163 correlated with longer patient survival.
“The CD8 to CD163 ratio appears to be a highly significant predictor of survival,” said Dr Keane.
“The findings are striking and it shows how our immune system can help protect us from lymphoma and contribute to some patients being cured of their disease.”
In addition, Dr Keane also found the ratio of CD8 with another immune-checkpoint PD-1 was strongly prognostic.
In this research project, Dr Keane is validating his initial results in DLBCL as well as assessing the CD8:CD163 ratio in predicting survival in patients with follicular lymphoma, Hodgkin lymphoma, post transplant lymphoproliferative disorder and HIV-related lymphoma.
He aims to develop a reliable test to predict if a patient’s immune system is capable of eradicating their cancer with standard therapy.
“If we can accurately demonstrate that someone is likely to fail standard treatment, it will allow their clinician to develop a new treatment strategy.
“I suspect that these patients may benefit the most from immune checkpoint therapies. To prove this, I’m using laboratory models to investigate which lymphoma subtypes respond to these new therapies.”
The Leukaemia Foundation awarded a Clinical Fellowship to Dr Keane in 2009.