Encouraging the immune system to increase the body’s anti-tumour activity, a process called immunotherapy, has transformed the management and outcomes for patients with advanced melanoma. The development of  compounds that prevent tumours from growing, called checkpoint inhibitors, has achieved unprecedented results and changed the landscape for patients with many solid tumours. Accelerated approval and access to  immunotherapy has led to areas of active research in improved patient selection and the identification of additional pathways for targeting. A collaboration between Consultant Medical Oncologist Dr Helen Winter and Chair in Translational Immunology Professor Linda Wooldridge in Bristol Veterinary School is exploring the role of a specific type of white blood cell, known as a T cell, in cancer and the impact of checkpoint inhibition. 

The research is looking for genes and proteins (biomarkers) that can provide more information about the cancer. Identifying these allows us to predict how effective our checkpoint inhibitors are in the treatment of metastatic melanoma patients which, in turn, helps us understand the mechanisms that resist checkpoint blockades and determine alternative approaches that would make the therapy more effective. This research collaboration explores why some patients fail to respond to immunotherapy and identifies predictive biomarker and additional pathways that may be targeted to improve response and overcome resistance .

As the Bristol lead on the Microbiome Immunotherapy Toxicity and Response Evaluation (MITRE) study, Dr Winter and colleagues are also investigating the role of the microbiome with immunotherapy treatment. This is specifically looking at the gut microbiome ‘signature’ to see if it can predict for immune checkpoint inhibitor treatment efficacy in patients with advanced cancers.

https://www.swagcanceralliance.nhs.uk/

Publications: 

• Wilson TG et al. (2021). Treating brain metastases in melanoma: What is the optimal CNS-directed and systemic management? Journal of Radiosurgery and SBRT.
• Wilson T et al. (2021). Sequential immunotherapy in melanoma: is it a realistic alternative to dual immunotherapy? Melanoma Research.
• Corrie P et al. (2021). Identification of a microbiome signature predicting immune checkpoint inhibitor outcomes across multiple cancer types. Journal of Clinical Oncology.