Systems immunology approaches to dissect the role of tertiary lymphoid structures in cancer

The formation of high-quality germinal centres (GCs) is paramount to developing antibody responses central to resolving disease. How these antibodies are generated in such an efficient and well-regulated manner relies on a controlled and compartmentalised immune-regulatory environment to prevent the production of self-reactive autoantibodies. Reduced GC function has been widely reported in infection, autoimmune diseases, and ageing. Advancing our understanding of the cellular processes curtailing the host immune-regulatory environment modulating GCs could have a clinical impact.

Over the last couple of years, evidence has emerged revealing the presence of T-cell-B-cell-rich tertiary lymphoid structures (TLS) close to tumour cells have been associated with overall survival and better response to immunotherapy in cancer, suggesting an immune benefit. Yet, their interindividual variation in cellular composition, spatial organisation, and the immune mechanisms regulating humoral responses remain unclear. 

With more than ten years of expertise in the HIV field with a focus on the biological processes underpinning the regulation of humoral responses, the Functional Immunology lab led by Dr Pedroza-Pacheco aims to translate their established methodologies to systematically quantify the functional relationship between tumour-intrinsic molecular processes, and the formation, cellular composition, and spatial distribution of CD4-B-cell-rich TLS within the tumour microenvironment. Understanding how CD4 Tfh and B cells contribute to anti-tumour responses provides an exciting opportunity for their translation into precision immunotherapies, non-invasive biomarkers, and cancer vaccines.