Tell us about your research.
A major focus of work in my lab is to find new ways to control inflammation in order to develop better treatments for people with cancer.
The project funded by OCION examines one particular type of immune cell: macrophages. These cells are found at high levels in many tumours including breast, brain, colorectal, head and neck, pancreatic, lung and liver cancer.
Typically, the higher the number of macrophages in these tumours the worse the outcome for the patient. However, whilst it has been known for some time that these cells are associated with poor survival, there are currently no available drugs that effectively target macrophages. This is because it is not fully understood how they help tumours to grow.
Our research has found that macrophages help tumours grow using a protein called F4/80. This protein sits at the surface of every macrophage, where it switches on other immune cells called Tregs. Tregs protect tumours, preventing cancer from being destroyed by our natural immune response. This action of F4/80 is essential for cancers to survive, without it tumours cannot grow well or spread.
What are the potential implications of this work for patients?
Our goal is to develop drugs that stop macrophages from turning on tumour-protecting Tregs. In this way we hope to re-instate destruction of the tumour. These drugs have the potential to be effective across a wide range of tumour types, and in large numbers of patients, who we can quickly identify for treatment at biopsy by counting macrophage numbers in the tumour. They should be safer than existing immunotherapies, which turn on immune cells that attack both cancer and healthy tissues indiscriminately.
What do you think are the major obstacles for the cancer field to overcome in the next 10 years?
We know that the extracellular matrix plays a key role in tumour progression and is a major determinant of patient treatment response. However, current strategies that target the matrix have been largely non-specific and can lead to serious side effects, including accelerated tumour metastasis.
Alternative treatment strategies at the moment are limited because we do not have a comprehensive understanding of how the matrix changes from very early pre-lesional stages to well evolved tumour sites, nor of the impact of these changes on cell behaviour.
Dissecting these complex pathways and unpicking pathogenic cell-matrix interaction networks, and moving new matrix-targeting treatment strategies towards clinical trials, could lead to game changing ways to diagnosing stratifying and treating people with cancer over the next decade.
What does Oxford Cancer and OCION mean for you and your research?
Oxford Cancer and OCION provides a fantastic network of fundamental and clinician scientists, and patient partner groups, all with the singular uniting aim of developing better treatments for people with cancer. Being part of this critical mass opens up access to expertise across a wide range of disciplines; this has accelerated our own cancer research by providing world class collaborations, technologies and patient cohorts.
Kim is a Professor of Matrix Biology and principal investigator at the Kennedy Institute. She has a long-standing interest in understanding how the extracellular matrix (a complex network of molecules that provide structural and biochemical support to cells within organs) dictates well-controlled immune responses. She examines how these processes go wrong in autoimmune diseases and in cancer, and develops new therapies that target mis-regulated environmental cues to restrain or retrain inappropriate inflammation.
Read more about her work on her NDORMS Profile.