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Functional differences in neutrophils

It's What's Inside That Counts: Neutrophils Form Distinct Subtypes

Dortmund / Duisburg / Essen, 29th June 2026

Neutrophil granulocytes are the first responders of the human immune system and constitute the largest population of white blood cells. Researchers at the Faculty of Medicine at the University of Duisburg-Essen and the Leibniz-Institut für Analytische Wissenschaften – ISAS – have now demonstrated in Advanced Science that neutrophils can be divided into two distinct subpopulations with completely different functions. There are neutrophils that express the surface protein CD177 on their outer membrane, and others which, although they possess a functional gene for CD177, do not utilise it. The presence of this surface protein has an impact on disease progression. Until now, CD177 was generally regarded merely as a marker of activity or maturation for neutrophils.

“Our data show that CD177-negative neutrophils are present on a permanent basis. In this cell population, the gene is consistently not expressed, meaning they never produce the CD177 protein tm. They therefore do not represent a transitional or maturation stage, but rather a genuine, stable subpopulation”, explains Marcel Jung, doctoral researcher at the Institute for Experimental Immunology and Imaging. Humans have very different proportions of CD177-positive and -negative neutrophils in their blood, which can range from 0 to 100 per cent. Until now, these neutrophil subtypes were thought to be functionally indistinguishable, as they are morphologically identical.

Disease-relevant functions of CD177

For the first time, the researchers have now been able to demonstrate, using a new integrated proteomics and lipidomics analysis, that the molecular signatures in
CD177-defined neutrophils differ significantly from one another: CD177-positive and
-negative neutrophils in the blood fulfil entirely different functions. As a result, they also play different roles in disease progression, for example in strokes or head and neck tumours. In head and neck tumours, the researchers were able to demonstrate that CD177⁻ cells accumulate in the tumour tissue. Unlike CD177⁺ cells, CD177⁻ cells have no anti-tumoural effect. This is associated with poor clinical outcomes for patients.

About CD177

A significant proportion of the population completely lacks this protein – so-called CD177-deficient individuals do not possess a functional gene. Although most humans produce CD177, the gene is only actively expressed in a subset of neutrophils. As a result, both CD177-positive (CD177⁺) and CD177-negative (CD177⁻) neutrophils circulate in the blood at the same time. The proportion of CD177⁺ cells remains constant over long periods, regardless of circadian rhythms, disease processes or experimental stimulation in the laboratory.

CD177 in diagnosis and treatment

“Our findings raise the hope that the ratio of CD177⁺ to CD177⁻ neutrophils could be used as a biomarker in the blood to assess the risk of progression of head and neck tumours or complications following a stroke,” says Prof. Dr Matthias Gunzer, project leader at the DFG SFB TRR 332 “Neutrophils: Origin, Fate and Function” and head of the Biospectroscopy department at ISAS. At the same time, the finding that CD177⁻ cells possess pro-tumoural properties opens up new targets for therapeutic strategies by specifically modulating this subpopulation or blocking its harmful activities.

Link to the original publication

CD177 deficiency defines a stable subtype of human neutrophil granulocytes with tumor promoting activity. https://doi.org/10.1002/advs.76236

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