IPP Group | Functional Immunology
"Dissecting the functional role of antibodies and how they are regulated is critical to improving patient's treatment" Dr Isabela Pedroza-Pacheco
The overarching goal of the Laboratory for Functional Immunology is to improve our understanding of cellular and molecular mechanisms underlying the regulation of germinal centre responses in vaccination, infection, and cancer, to dissect mechanistic targets that could be used to improve vaccines and therapeutic strategies.
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 (autoAbs). 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.
Immune "environment" underpins HIV broadly neutralising antibody responses | Learning from a subset of patients who develop bnAbs
Assisted by the application of novel technologies and the development of methodologies, the IPP lab uses a holistic systems immunology approach that combines viral and host factors, global antibody repertoire, autoAb prevalence, and transcriptional/functional profiling of key cellular GC features from the bottom up. As part of the CHAV-D Consortium, this work has provided insight into the mechanistic function of CD4 regulatory T cells (Tregs), T follicular regulatory cells (Tfr), Natural Killer (NK) cells, and regulatory B cells (Bregs) in modulating CD4 Tfh and B cells in humans using in vitro assays while uncovering predictive cellular features of the presence of bnAbs in chronic HIV infection. This predictive immune "signature" will be tested in future phase I clinical trials of HIV vaccination.
Applying our methodologies to cancer | What is the role of antibodies and B cells in cancer?
Over the last couple of years, evidence has emerged revealing the potential role of antibodies with diagnostic and/or therapeutic potential in cancer. High prevalence of endogenous antibodies that can directly bind tumour surfaces and the presence of B-cell-rich tertiary lymphoid structures (TLS) close to tumour cells have been independently 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 tumour-specific antibodies remain unclear.
With more than ten years of expertise in the HIV field with a focus on the biological processes underpinning the regulation of antibody responses, the IPP lab 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 B-cell-rich TLS within the tumour microenvironment associated with tumour-reactive antibodies. Understanding how antibodies and B cells contribute to anti-tumour responses provides an exciting opportunity for their translation into precision immunotherapies, non-invasive biomarkers, and cancer vaccines.
Dr Pedroza is part of the Duke Consortia for HIV/AIDS Vaccine Development (CHAVD) and the Oxford Cancer Research Initiative, Oxford Cancer.
Further information about DPhil projects is available on the CSC - CAMS/PUMC Programme.