WEHI Wednesday Seminar hosted by Professor Joanna Groom
 

Raymond Qin
Research Officer | PhD Student – Groom Laboratory, Immunology and Centre for Dynamic Imaging, Advanced Technology & Biology divisions, WEHI

Defining the Cellular Networks of Murine Tumour Tertiary Lymphoid Structures

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

Tertiary lymphoid structures (TLSs) are organised immune aggregates developed in the non-lymphoid tissues at site of chronic inflammation. TLS are thought to be functionally similar to secondary lymphoid organs and provide local immune responses. In human cancers, TLSs are comprised of highly organised immune cells and stromal cells with production of cytokines and chemokines to regulate their functions. The development of TLS correlates with enhanced responses to immune checkpoint blockade immunotherapy. Therefore, the presence of TLSs has emerged as a novel prognostic marker for cancers and therapies outcomes. However, the absence of TLSs in conventional mouse tumour models, particularly subcutaneous injection models, limits our mechanistic understanding of TLS and our ability to promote TLS development.

During my PhD, I have overcome this challenge to describe a mouse subcutaneous tumour model that naturally forms TLSs within the tumour-associated-stroma. We characterised the chemokine environment in this niche and identified the chemokine, CXCL9 as a key regulator. CXCL9 deficiency reduced the efficacy of immune checkpoint blockade immunotherapy. Furthermore, single cell RNA sequencing revealed key interactions between T lymphocytes and antigen presenting cells, indicating a CXCL9-dependent cellular contact in tumour and TLS. Finally, to understand the immune cell migration processes in this environment, we developed a microfluidic device to deconstruct these complex chemokine environments and investigate cells’ 3D morphological changes in vitro. By combining these models and technologies, my PhD has advanced our understanding of TLS formation and maturation and provides essential information on how these structures can be promoted to enhance cancer therapy.

All welcome!