A UCLH and UCL study has identified how a subset of immune cells are activated to kill cancerous cells, a finding in mice which could hold the key to new powerful therapies against cancer.
The study led by Professors Sergio Quezada (UCL Cancer Institute) and Karl Peggs (UCLH and UCL Cancer Institute) built on the authors’ previous research which found that following immunotherapy some cells traditionally thought to be ‘helper’ and ‘regulator’ immune cells – known as CD4+ T cells – in fact directly engage with and kill cancer cells.
For this new study, published in the journal Immunity and funded by Cancer Research UK, researchers examined the molecular and cellular mechanisms underpinning this activity.
Researchers found that a ‘growth factor’ for T cells known as IL-2 and the ‘transcription factor’ Blimp-1 are responsible for initiating potent killer activity in CD4+ T cells within cancerous tumours.
Co-lead author, Professor Sergio Quezada (UCL Cancer Institute), said: “We knew these immune cells had the ability to proactively kill cancer cells with incredible potency, but to maximise their potential, we needed to know how this mechanism was activated.
“Our discovery provides the evidence and rationale for utilising Blimp-1 to maximise the anti-tumour activity of CD4+ T cells.
“Work is now underway in our lab to develop new personalised cell therapies where the activity of Blimp-1 can be maxed up to drive potent tumour control.”
T cells play a key role in the body’s immune response. In immunotherapy T cells are modified and used to attack cancer. These cells move around our bodies, looking for infected cells and killing them. However, T cells do not recognise most cancers, since cancers develop from our own tissues and appear normal to most T cells. The main challenge with T cell immunotherapy approaches is to find ways to direct T cells to attack cancer cells.
Co-lead author Professor Karl Peggs of UCLH and UCL said: “Cellular therapies have only recently entered the mainstream in terms of clinical application.
“Much remains unknown regarding how best to optimise these therapies, particularly to enable better activity in solid organ cancers.
“Our findings broaden our understanding of the regulators of T cell differentiation, illuminating new elements that might be targeted to enhance therapeutic efficacy.”