David Withers

Inspired by exposure to immunology during undergraduate studies at the University of Warwick, I undertook my PhD at the Institute of Animal Health, Compton in 2000, investigating chicken B cell development and how this was impacted by neonatal infection. This early training in comparative immunology taught me the importance of assessing cellular changes within tissue microenvironments, as well as the value of thinking creatively in designing experiments when the perfect reagents are limited. Determined to develop my expertise in studying the human immune system, I then undertook post-doctoral training at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health, Bethesda, MD. Within the Autoimmunity Branch of Dr Peter Lipsky, I studied human B cell development and approaches to target human plasma cells. 

In 2006, I returned to the UK, undertaking further post-doctoral studies in the laboratory of Professor Peter Lane, situated within the MRC Centre for Immune Regulation at the University of Birmingham. Surrounded by experts in seemingly all facets of immunology, this was a really exceptional environment in which to continue my training. My research was focused on understanding the regulation of CD4 T cell responses within secondary lymphoid tissue and testing the hypothesis that lymphoid tissue inducer cells played a critical role through provision of specific costimulatory signals. The realisation in the late noughties that lymphoid tissue inducer cells were part of a wider family of innate lymphoid cells, helped fuel the explosion of interest into what this newly identified arm of the immune system contributed in health and disease.

In 2011, I was awarded a Wellcome Trust Research Career Development Fellowship to establish my own group, continuing my studies of innate lymphoid cells and their regulation of T cell responses in lymphoid tissues. Initial progress was rewarded with a Wellcome Senior Research Fellowship in 2016. Supported by an excellent team of PhD students, post-docs and collaborators, my research investigated how different innate lymphoid cells regulated adaptive immunity in different tissue environments. How cellular interactions at different sites combine to orchestrate optimal T cell responses continues to underpin my research.  

As we investigated the regulation of T cell responses in different tissues, I became increasingly interested in the tumour microenvironment and how this subverted immune cell functions. To track how immune cells changed having entered tumours, we pioneered photo-labelling approaches, supported by funding from Cancer Research UK, the Cancer Research Institute and Worldwide Cancer Research. Dynamic analyses of how the immune composition of cancers is established and maintained have become a major research theme within the lab. In 2023, I was awarded a Cancer Research UK Discovery Programme focused on understanding suppressive mechanisms within colorectal cancer. The lab is further supported by a team-based Wellcome Discovery Award (CoApplicants: Professor Menna Clatworthy and Dr Sophie Acton) focused on determining the mechanisms controlling tertiary lymphoid structure formation and how these immune aggregates can be manipulated for therapeutic benefit. In 2024, I joined the Centre for Immuno-oncology at the University of Oxford as a Group Leader in Experimental Cancer Immunology.