Lung cancer is a devastating disease causing 1.8 million deaths worldwide every year. Immunotherapy is a type of treatment that increases the elimination of tumour cells by an individual’s own immune cells. Immunotherapy has dramatically improved the survival of many lung cancer patients. However, only a small proportion of patients respond to this type of therapy.
To identify new ways to improve response to immunotherapy, we need a comprehensive understanding of the communication between tumour and immune cells. The Asselin-Labat laboratory uses novel approaches that integrate spatial information with molecular characterisation and genomic screening to achieve this goal.
Our research focuses on studying the lung epithelium and the role of surrounding immune cells in maintaining lung health and controlling lung cancer formation. We work with preclinical models as well as clinical samples to assess the role of immune cells in maintaining lung homeostasis. We investigate mechanisms developed by tumour cells to escape immune surveillance. Our aim is to identify ways to reactivate immune activity against cancer cells with the ultimate goal to improve outcomes for people with lung cancer.
3D OPT imaging showing Keratin 5 expression in Ezh2 cKO embryonic lung
Our mission
Our laboratory mission is to build a world where every lung cancer patient receives effective therapy. Our research vision is to empower the immune system to better recognise and target cancer cells by integrating the molecular traits and spatial features of tumour cells and their microenvironment, to ultimately deliver personalised, effective treatments that improve patient outcomes.
Impact
Recent discovery: We uncovered a new role for lung tissue resident memory T cells in accelerating immune evasion mechanisms in tumour cells, through deep exploration of human datasets and in vivo animal studies. These findings identify that the ‘soil’ in which tumours are grown has lasting effects on tumour immunogenicity and therapy response, providing novel insight in mechanisms of immune evasion. Weeden et al., Cancer Cell 2023
Technics: Our apoproaches integrate molecular cell characteristics, genetic editing and spatial cell organisation using algorithms based on artificial intelligence to determine the state in which a cell resides and how cells transit between different states under the influence of surrounding cells. We exploit spatial proteomic (MIBIscope), spatial transcriptomics, CyTOF, proteomics, genomics, CRISPR/Cas9 editing to uncover mechanisms regulating tumour evolution.
Lab research projects
Using human lung tissue samples, we aim to identify recurrent neoantigens present by tumour cells to the immune system. This project uses proteomic and transcriptomic approaches to identify neoantigens and in vitro assay to determine their immunogenicity.
Mechanisms of resistance to immunotherapy include tumour intrinsic and extrinsic factors mediated by the tumour microenvironment. The project aims to characterise the interactions between immune cells and tumour cells in NSCLC to understand resistance mechanisms and propose new targets for the development of therapy.
The project combines spatial molecular profiling and in situ imaging analysis with genetic studies in preclinical models of NSCLC and in clinical samples.
Silencing the antigen presentation machinery is a known mechanism invoked by tumour cells to evade the immune system. Using CRISPR/Cas9 screening approaches, we aim to identify pathways regulating the antigen presentation machinery in lung cancer. Our goal is to identify targets that could be exploited therapeutically to increase tumour cell visibility.
Lab team
My research group has established collaborations with Professor Daniel Gray, Associate Professor Kate Sutherland and Professor Marnie Blewitt.
Enquiries from prospective Honours or PhD students, including clinicians interested in research, are welcome.