The moment immune system spots cancer to be pinpointed in pioneering University of Cambridge study
A new University of Cambridge study aims to pinpoint for the first time the very moment the immune system recognises a tumour.
The research team will receive more than £1.5m from Cancer Research UK over six years to investigate how the immune system evolves, targets and kills cancer cells as tumours are developing, with the aim of helping to catch cancer earlier than ever before.
Cancer is usually diagnosed when tumours are already developed, meaning treatment is usually required to remove them and prevent further growth.
But if the team can detect the trigger point when our own body starts to recognise cancerous cells, it may help identify a way we can use immunotherapy treatments to spark our own immune system to kill cancer cells before tumours can form.
Heather Machado, who leads a team in the Department of Pathology, studies T cells, which fight infection and disease. The study will examine how they respond to cancer when they first recognise and respond to a tumour in the kidneys or the liver.
Dr Machado said: “Using mutations that naturally accumulate in each of our cells as we age, we can essentially build a family tree of T-cells, and this family tree has information about when T-cells met cancer for the first time.
“This research is only now possible as a result of advancements in DNA sequencing technology. This research has the potential to give an entirely new perspective on the role of the immune system in cancer progression, findings that we hope to use to further improve lifesaving cancer immunotherapies.
“Most cancers are diagnosed years or decades after early tumour development, which can often be too late. Our methods will allow us to go back in the cancer’s timeline to understand the immune response in these early stages of cancer development.
“Beyond improving immunotherapies, we hope that this understanding helps us detect cancer earlier, at stages where survival rates are much higher.”
The early immune response in humans has been difficult to study.
Dr Machado will use genome sequencing to explore how a tumour and the immune cells co-evolve over the course of tumour development.
She explained: “I will time T cell clonal expansions using evolutionary trees built from the genomes of individual T cells, exploiting recent advancements in single-cell whole genome sequencing. I will perform these experiments using early-stage kidney and liver cancer resections and by sampling throughout the course of immunotherapy in metastatic kidney cancer.
“The study is believed to be the first of its kind in the world and it has the potential to be groundbreaking research as we have never been able to examine these evolutionary dynamics in humans before.
“How long before a tumour is diagnosed has the immune system been responding is an incredibly hard problem to solve because these immune dynamics play out years prior to diagnosis.
“Normal cells evolve into tumours, and we are blind to much of that process and yet the immune system is one of our best tools for fighting cancer.
Dr Machado, who studied for her PhD at Stanford University and completed her postdoctoral research at the Wellcome Sanger Institute in Hinxton, continued: “This research funded by Cancer Research UK leverages my unique background, as it lies at the intersection of evolution, genomics, immunology and cancer biology. It is really exciting because we are using cutting edge technology that is only available now and we are going to be able to discover how the immune system responds to tumours unlike we have ever seen before and that is potentially life-changing, in terms of improving immunotherapies for better health and patient prognosis.”
