• PANCREATIC CANCER
• IMMUNE RESPONSE

A hallmark of cancer is chronic inflammation.1 In turn, inflammation is driven by heterogeneous, often antagonising, immunological cues that contribute to multiple stages of cancer, from oncogenic transformation to metastatic spread.2 Single-cell RNA sequencing technologies have enabled the identification of common as well as distinct immune profiles across tumour types with unparalleled resolution,3 thereby enabling the development of promising immunotherapeutic strategies. The amount of single-cell studies published in recent years, however, is overwhelming, with increasing public databases building up our understanding of the tumour microenvironment but also creating a degree of confusion as many of those studies are largely descriptive. This is particularly relevant when single-cell transcriptomics are applied to study poorly transcriptional cells, such as neutrophils, which are often lost during sample processing or simply wrongly annotated.

At the core of this technical limitation lies the unique biology of these cells: neutrophils feature short life spans, low transcriptional activity and low abundance in certain tissues and physiological contexts, altogether explaining why they have been missed or neglected in conventional single-cell analytical pipelines, especially in human samples.4 This can be problematic, as these leukocytes dominate the immunological landscape of many solid tumours and have been associated with poor disease outcomes in patients with cancer.5 Further, recent studies have demonstrated that neutrophils, like other myeloid cells, are highly heterogeneous and capable of transcriptional rewiring, …