Judith Ramage - Tissue Resident immune cells in Breast Cancer
2019 Pilot Grant
Lay summary
Cancer patients can make an immune response to their cancer in a similar way as to an infection. This infection does not come back as the immune system remembers the infection. In most cancer patients the immune system cannot fight off the cancer. This is because the cancer puts "the brakes on" the immune system. Recent therapies have taken the breaks off the immune system. This means that they are now able to kill the cancer. These therapies are now curing cancer patients. However, not all patients respond as well to these therapies. We do not fully know the reasons for this. We do know that the patients that do respond have made an immune responses to their cancer. It is important that we study this further in order to improve therapies for all cancer patients. We will study the immune cells of breast cancer patients by looking at the ones that are present in the cancer. We can look at seven markers in the tumour at the same time. This means we can look at the immune cells and how they interact with other cells in the tumour. We will then be able to show how the presence of these cells effects patient’s survival
Scientific summary
There has been a step change in oncology with the realisation that immunotherapy can and does cure cancer. Immune checkpoint blockade (ICB) therapy has cured patients who previously had little chance of surviving. Patients with a pre-existing immune response have been shown to respond better to these therapies. Indeed, T-cell infiltration into tumours is superior to tumour staging in predicting patient survival. Recently, CD103+ tumour infiltrating lymphocytes have been shown to be a better predictor of survival than CD3 or CD8 in a number of cancers including breast cancer. CD103 is a marker of tissue resident T-cells (TRM). However, CD103 is present on a number of different cells and multiple markers are required to accurately determine the phenotype of TRM. We aim to study the biology/phenotype of the TRM in situ in breast cancer using multiplex imaging to comprehensively analysis the phenotype of these cells within the tumour environment and determine their effect on patient survival. The benefit of studying TRM by multiplex immunohistochemistry is that we can investigate the importance of anatomical micro-location and interactions with other cells in the tumour microenvironment. This proposal has the potential to aid with both prognosis and the treatment of breast cancer.