Tell us about your role.
My main role is to coordinate and supervise translational research in the field of tumour immunology and immunotherapy. In the Oxford University-hospitals ecosystem there are multiple wonderful opportunities for synergistic collaborations from basic discovery research to proof-of-concept clinical trials. My ambition is to help make the most of them.
Tell us a little about your research focus.
For a cancer to survive it must evade anti-tumour immune responses which can recognise and kill cancer cells. My research has focussed on how to increase these natural anti-tumour responses, but also how we can remove negative influences. Over the years we have focused on several immune modulators that boost anti-tumour activity including factors such as CD137 agonists and interleukin-12.
We have also discovered types of inflammation in tumours that are deleterious to anti-cancer immunity. Such pro-tumour functions are orchestrated by soluble inflammatory mediators whose functions can be therapeutically neutralised. Two of them – TNF and interleukin-8 – are of particular interest because neutralising them enhanced efficacy of other immunotherapies including checkpoint inhibitors. In the clinic we have tested several combinations of immune-targeting drugs since the beginning of the immunotherapy revolution and keep doing so. Our favourite word is synergy and the adjective synergistic.
In mouse and human systems we study and dissect mechanisms to understand how to increase the efficacy of immunotherapy. One of them termed ‘cross-presentation cross-priming’ of tumour antigens by a subset of dendritic cells (type-1 dendritic cells) has fascinated us. Without these minority cells, no known immunotherapy works in the rodents. In human tumour tissue, the number of these cells are inversely correlated with the efficacy of immunotherapies. We now intend to enhance their numbers and function in contexts where immunotherapies are only attain partially effective.
What are the potential implications of this work for patients?
The implications are already there. We are observing responses in clinical trials. We want to improve results (Citius, Altius, Fortius: Faster, Higher, Stronger) via several strategies. Some of the treatments we started in advanced liver cancer for instance seem to benefit one third of the patients reaching 5-year survival. Our goal here is to identify who benefits and why others are unresponsive. We also try modelling in the laboratory and mouse models with the ultimate aim of improving results.
How important are collaborations for your research?
Critical. I need multidisciplinary expertise: pathologists, bioinformaticians, proteomics experts. We should offer models and samples to others. It takes a village to advance the field, and Oxford should aspire to achieve breakthroughs. Alliances/liaisons with pharmaceutical and biotech companies is also a key aspect for success.
What do you think should be the priorities for the cancer field in the next 10 years?
I am afraid that I am biased: harnessing the power of the immune system to treat cancer. More technically speaking this involves immunogenic cell death, cross priming, inhibiting the wrong type of inflammation in tumours, exploiting dendritic cell co-stimulation, targeted therapies to key molecules of the immune system, combinations with antibody drug conjugates and T-cell engagers, combinations of vaccines and adoptive T-cell therapy, understanding lymphocyte traffic to tumours, harnessing hotspot oncogene-encoded neoantigens. But let us not forget that in 10 years many discoveries will be made.