Major advances in our understanding of cancer biology have been translated into new treatment options for patients, including immunotherapy.

Cancers develop numerous ways of hiding from the immune system or reducing its activity. Immunotherapies are used to harness and enhance the immune system to recognise and attack cancer cells. However, patients often respond differently to treatment depending on the genetic make-up of their disease.

Our Melanoma Immunotherapy Research Programme is investigating some of the reasons why tumours respond to or are resistant to immunotherapy. Through analysing samples and looking at their genetic make-up, the aim is to understand how cancer cells can evade detection from the immune system and why certain patients respond well to treatment and why others do not. 

Diagram of lung and brain tumour evolution.

Cancer is caused by genetic mutations. These mutations can evolve throughout the life of a tumour. This evolutionary process can result in genetic variations both within a single tumour and between metastatic tumours, known as intra tumour and inter-metastatic heterogeneity.

It is this heterogeneity that poses major challenges to effective treatment, especially given the dynamic interaction between the genome (DNA) of a cancer and the immune system. Research into evolutionary processes can allow for a better understanding of the causes and progression of the disease, as well as help inform optimal timing of treatments and identify new treatment opportunities for patients. 
 
This programme is leveraging recruitment from two complementary studies. Through analysis of genetic information, often longitudinally, the Melanoma TRACERx study seeks to understand the variation in response to treatment. The second is the PEACE study, a post-mortem study enabling sampling of tumour at multiple metastatic sites following multiple lines of immunotherapy and targeted therapy.

Funders

  • Skin & Renal Unit at the Royal Marsden NHS Foundation Trust
  • Royal Marsden Cancer Charity (significant donations from Ross-Russell Family, MacFarlanes LLP and Shiona Ramage)
  • McAlpine Foundation
  • Melanoma UK