COI Project 6: Characterising tumour-reactive T cells in lung cancer patients undergoing immune checkpoint inhibitor therapy

About the Project

Lung cancer remains one of the leading causes of cancer-related mortality worldwide. Despite recent advances, including the use of immune checkpoint inhibitors (ICIs), only a subset of patients achieves durable responses, and predictive biomarkers of benefit remain limited. Tumour-reactive T cells—lymphocytes that specifically recognize and tumour antigens and kill the tumour cells—play a pivotal role in mediating the effectiveness of immunotherapy. However, their phenotypic and functional characteristics in cancer micro-environment, how they interact with cancer cells and other cells in the micro-environment and how these are modulated by ICI treatment are largely unknown. Understanding the biology of these cells may uncover novel biomarkers and therapeutic strategies to improve patient outcomes.

In this study, we aim to characterise tumour-reactive T cells in a cohort of lung cancer patients receiving immune checkpoint inhibitors and to investigate how these cells shaped by therapy. Using the well-established pipelines in our Lab, including multiomic single-cell analysis and spatial TCR/transcriptome profiling that enable investigation of antigen specific T cell within tissue, we will profile the phenotype, clonality, functional state, and tumour specificity of circulating and tumor-infiltrating T cells before and after treatment, and correlate these features with clinical outcomes (response, progression-free survival, overall survival) to identify biomarkers of benefit and mechanisms of resistance.