Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare and aggressive cancer strongly associated with Epstein–Barr virus (EBV). While the tumour microenvironment is increasingly recognised as an important contributor to the disease, how tumour cells and surrounding immune cells interact and organise within ENKTL tumours remains poorly understood.

In this study, published and featured in the journal Leukemia, Prof Ng Siok Bian, Dr Anand Jeyasekharan, Dr Leong Sai Mun and first author Deng Li Chang, together with their teams, used spatial transcriptomic, proteomic and single-cell imaging approaches to map the ENKTL tumour microenvironment. They identified two distinct ENKTL subgroups defined by their macrophage populations and immune activity. Notably, they uncovered an inflammatory niche in which a specific NF-κB-associated tumour cell population co-localises and interacts with inflammatory myeloid cells. A higher abundance of this niche was associated with better survival.

The findings provide new insights into how tumour and immune cells cooperate to shape ENKTL and offer a spatial framework for developing future biomarkers and more precisely targeted immunotherapeutic strategies.

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