When Naomi van den Berg graduated from Darwin with a PhD in mathematical modelling last year, cancer research was not a field in which she had much experience. Her PhD had focused on the interaction dynamics of microbes, while before coming to Cambridge she had completed a BSc in Environmental Sciences at the University of Utrecht, and an MSc in Resource Ecology at Wageningen University.
But last year she took up a role as a Postdoctoral Fellow at the Francis Crick Institute, conducting mathematical modelling into cancer dynamics. In research published this week in the journal Cancer Cell, she presents a new theory of how tissue metabolism shapes the immune response to cancer.
In a concept she has termed immunometabolic gatekeeping, Naomi suggests that the metabolic properties of healthy tissues – how much energy they use and how well they clear metabolic waste – help determine how effective immune responses can be, even before cancer develops.
“Cancer research was very new to me, and with fresh eyes, colleagues and I developed a novel cancer synthesis,” Naomi explains.
“The theory aligns several cancer paradoxes; including why solid cancers in children are confined to specific organs, why men get tumours more frequently than women, why large animals are cancer-resistant, and more.”
Naomi’s research could help to explain patterns that have puzzled cancer researchers for years. In cancers such as melanoma or colorectal cancer, high T cell infiltration is linked to good outcomes. But in cancers arising from metabolically intense tissues, including renal cell carcinoma, brain tumours, and uveal melanoma, high immune infiltration does not reliably predict better survival, and sometimes correlates with worse outcomes.
In these tissues, immune cells may enter tumours but fail to function properly because they are operating near their metabolic limits from the start. As tumours grow, they further increase metabolic stress by competing for nutrients and producing additional waste, pushing immune cells into exhaustion.
For Naomi, attracting the attention of Cancer Cell has been a thrilling vindication of her decision to refocus her research interests.
“I am especially excited about it because it shows that even a saturated research field like cancer still has opportunities for novel concepts, and that switching fields after your PhD can be incredibly rewarding.”
