14 Jul 2025

Dr. Evangelos Giampazolias,

Group Leader, Cancer Immunosurveillance Group,

CRUK Manchester Institute, The University of Manchester

I have always been fascinated by the puzzle-solving nature of research, those moments when an unexpected result slowly starts to make sense. But just as important to me is the translational potential of the science we do. Working in cancer immunology has allowed me to combine both: dissecting fundamental process of host immunity using cells and mouse models whilst opening doors to explore therapeutic opportunities that might one day improve patient outcomes.

My scientific journey began in Athens, where I studied my undergraduate in Chemistry, followed by an MSc in Clinical Biochemistry. In 2012, I was awarded a 4-year PhD fellowship from Cancer Research UK (CRUK), which brought me to the CRUK Beatson Institute (now the CRUK Scotland Institute) in Glasgow. Under the supervision of Professor Stephen Tait, I studied how cell death triggers immunity to cancer. I discovered that caspases - key enzymes orchestrating apoptosis, a programmed type of cell death often triggered by cancer therapies - suppress inflammatory signals in dying cells that are required to activate cytotoxic T cells (CTL), the cancer-killing arm of adaptive immunity. Triggering apoptosis in caspase-deficient mouse cancers enhanced anti-tumour T cell responses and significantly increased the tumour rejection rates (Giampazolias et al. Nature Cell Biology, 2017). For this work, I was honoured to have been recognised with the Institute of Cancer Sciences Prize (2017) and the CRUK Pontecorvo Prize (2018). 

Driven by a growing interest in how the immune system recognises damaged cells, I joined the lab of Professor Caetano Reis e Sousa at the Francis Crick Institute as a postdoctoral fellow. There, I focused on how dendritic cells, sentinel cells of innate immunity, sense dying cells via the receptor DNGR-1, which binds the actin cytoskeleton exposed from inside the cell upon death. Engagement of DNGR-1 enables dendritic cells to effectively process and present dead cell-associated antigens to CTLs, promoting their effector function. I discovered that secreted gelsolin (sGSN), a member of the extracellular actin-scavenging system, interferes with this process by masking actin filaments and consequently limiting DNGR-1 engagement. In mouse models, sGSN deficiency led to improved tumour rejection and immunotherapy response, in a DNGR-1- and CTL-dependent manner. These findings were supported by human data, showing that lower intratumoural sGSN correlates with stronger immune signatures and improved survival (Giampazolias et al. Cell, 2021). This work led to the granting of an Innovation Patent in 2022 to explore therapeutic targeting of sGSN as a way to boost immune responses to cancer.

Towards the end of my postdoc, I began investigating other components of the actin-scavenging system - and the results took my work in a wholly unexpected direction. In mice lacking Gc globulin, an actin-binding protein, we observed enhanced tumour immunity and improved responses to immunotherapy. Interestingly, these effects appeared to be unrelated to its role in actin clearance. This prompted us to revisit another, previously described function of Gc: its ability to bind vitamin D in the circulation and keep it away from tissues. We began to wonder whether increased vitamin D tissue availability might mediate the anti-cancer effects we were seeing. We found that indeed, mice fed a vitamin D-rich diet displayed enhanced anti-tumour immunity - and, remarkably, this trait could be transferred to other mice via faecal transplantation. This unexpected observation led us to investigate the role of gut-resident symbiotic microorganisms (the microbiota), found in the faecal matter, in modulating cancer immunity. Indeed, we discovered that the microbiota’s ability to instruct cancer immunity depends on vitamin D activity in the gut epithelium and not merely on the origin of the microbial species. In humans, higher vitamin D levels correlate with lower cancer risk, better immunotherapy response, and improved survival (Giampazolias et al. Science, 2024).

This pivot has shaped the focus of my independent research. In 2023, I established my lab at the CRUK Manchester Institute, supported by a CRUK Institute Award. Recently, I was awarded a Royal Society Research Grant (2023) and ERC Starting Grant (2024) to decode how nutrient-host-microbiome interactions shape cancer immunity in mice and humans. It’s an exciting time, and I’m lucky to work with a talented team of scientists as we chart this emerging landscape of how trans-kingdom interactions between commensal species and host cells define immune responses to cancer. Our work benefits from strong partnerships with The Christie Hospital, one of the leading oncology centres in Europe, and the wider University of Manchester research community, including the Division of Cancer Sciences and the Lydia Becker Institute of Immunology and Inflammation. My ultimate vision is to identify microbiome functions that predict immunotherapy response and can be targeted to overcome therapy resistance, which remains one of the biggest challenges in immuno-oncology. 

Receiving the BACR/AstraZeneca Young Scientist Frank Rose Award at this point in my career is both a privilege and a moment to reflect on my path so far - from studying the key building blocks of life (chemistry), to  fundamental cellular processes (cell death) and their sensors (immune system), and finally, on to unexpected insights into the complex interplay between the host and its “friendly neighbours” (the microbiome): all of which underpin the immune system’s defence against cancer. I’m deeply grateful to the BACR and AstraZeneca for this honour, and to the many people - mentors, collaborators, and lab members - who have shaped this journey. I am excited for the discoveries still to come. 

“One never notices what has been done; one can only see what remains to be done.” Marie Curie.
 

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