Metastasis remains one of the most formidable challenges in cancer research and clinical oncology.

Despite major advances in our understanding of primary tumour biology, the process by which cancer cells spread to distant organs – and crucially, how they survive and begin to colonize these new environments – continues to elude us.

A nurturing niche

The tumour microenvironment (TME) plays a pivotal role in cancer progression. It consists of a dynamic and heterogeneous mix of stromal cells, immune cells, signalling molecules, and extracellular matrix components.

In the context of metastasis, the TME can either suppress or support the survival of disseminated tumour cells. There is growing consensus that the TME is not just a passive backdrop but an active participant in shaping the fate of cancer cells. However, the dual nature of the TME – its ability to exert both anti-tumour and pro-tumour effects – adds a layer of complexity.

These functions are not static; they evolve over time and vary across different tissues and stages of disease. Understanding how disseminated cancer cells manipulate the TME to create a supportive niche is one of the key challenges in the field.

By studying how the TME changes during the early stages of metastatic colonisation, we hope to identify vulnerabilities that can be therapeutically targeted. Disrupting the supportive interactions between cancer cells and their microenvironment could be a powerful strategy to prevent metastasis before it becomes clinically detectable.

Immune focus

A major focus of our work is the immune landscape of the metastatic niche, particularly the role of innate immune cells. Myeloid cells – including macrophages, neutrophils, and dendritic cells – constitute the bulk of the immune component in metastatic sites. These cells are highly plastic and can adopt a range of functional states depending on the signals they receive from the tumour and the surrounding tissue.

Despite their abundance, the precise roles of different myeloid populations in early metastasis are still not completely understood. What signals guide their differentiation and activation? How do they interact with each other and with cancer cells to shape the metastatic niche?

We are working to map the recruitment dynamics of these immune populations, dissect their intercellular communication networks, and understand how these interactions influence the survival and proliferation of disseminated tumour cells. Our ultimate goal is to identify strategies that can block the establishment of a tumour-supportive niche.

By targeting the immune components of the TME, I hope it will be possible to impair metastasis formation at its earliest and most vulnerable stage.