Dr Nischalan Pillay
University College London
Awarded: £120,000
Completed
Sarcoma UK is investing in research leaders of the future. Our PhD programme aims to start a researcher’s career in sarcoma by funding a training fellowship.
The challenge
One type of treatment for sarcoma is immunotherapy, which works by helping the body’s own immune system recognise and attack cancer cells. In some cancers, these treatments have been life-changing for patients, but clinical trials of immunotherapy in sarcomas have shown mixed results.
In a specific subtype of sarcomas called Undifferentiated Pleomorphic Sarcomas (UPS), some patients respond very well, while others see little benefit.
How did this project tackle this challenge?
The team looked more closely at the biology of UPS tumours to try to understand this different response. Using genomic analysis, they discovered that up to half of UPS tumours have no immune cells inside them. This means these patients are unlikely to benefit from a common type of immunotherapy called immune checkpoint inhibitors, which rely on immune cells being present to work.
In tumours where immune cells are present, the cancer still find ways to ‘hide’ from them by disrupting key genes. The researchers found two main tricks the tumour cells use. Sometimes pieces of DNA are missing, which is called a genetic deletion. Other times, the DNA is chemically modified in a way that switches off important genes, a process known as DNA methylation.
What this means for people affected by sarcoma
These discoveries are important because they help identify which patients are most likely to respond and benefit from immunotherapy. They also deepen our understanding of how sarcomas interact with the immune system, opening the door to exploring strategies to stop the cancer from not responding to treatment.
Once these footprints can be identified in DNA, they can be used to identify which patients will respond to specific treatment, so patients are more likely to get the treatment which will be most effective for them.
