Grant: Project Grant

Lung cancer is the leading cause of cancer-related deaths worldwide. Recently, drugs that boost patients' own immune response against their cancer have offered hope but only about 20% of patients respond. Health professionals need better ways to predict who will benefit from these drugs, termed immunotherapies, and to find strategies to overcome resistance for those who do not benefit. One clue we have is that B cells, a type of immune cell that produces antibodies that can target tumour cells, are important for immunotherapy success. This project aims to unravel the role of B cells in immunotherapy by studying the organization of cancer and immune cells and the specificity of the targets they recognize in unique patient populations and using advanced technology. We will work with data from the TRACERx study in the UK, which tracks over 800 patients with early-stage lung cancer from time of surgery over treatment, and focus on patients who received immunotherapies. This cohort contains a rare subset of patients that consented to a research autopsy, offering an unprecedented look at immunotherapy response and failure. B cell biology will be assessed in detail, looking at how they interact with other cells in the tumour environment, and which interactions are associated with immunotherapy success or failure. Findings will be validated in Canadian populations of patients with lung cancer. By the end of the project, we will identify immune cell features that can predict which patients will respond to immunotherapy, and pinpoint new targets to boost these responses and overcome treatment resistance. The discoveries made will ultimately help guide more effective, personalized therapies for lung cancer patients.