CD177 Deficiency Defines a Stable Subtype of Human Neutrophil Granulocytes with Tumor Promoting Activity

  • Adv Sci (Weinh). 2026 Jun 22:e76236. doi: 10.1002/advs.76236.
Marcel Jung  1 ,  Alexander Beer  1 ,  Susmita Ghosh  2 ,  Ekaterina Pylaeva  3 ,  Belal Alshaar  2 ,  Tobias Tertel  4 ,  Nils Bastian Leimkühler  5 ,  Thomas Schroeder  5 ,  Janine Gronewold  6 ,  Nina Hagemann  6 ,  Ayan Mohamud Yusuf  6 ,  Benedikt Frank  6 ,  Yiqiao Zhang  6 ,  Dennis Nagel  1 ,  Kim Schloeßer  2 ,  Laura Karsch  1 ,  Emily Hedtfeld  1 ,  Sabrina Lohmann  1 ,  Kathrin Blank  1 ,  Andreas Kraus  1 ,  Max Krumbein  3 ,  Nastassia Kabankova  3 ,  Hongxiao Wang  2  7 ,  Almke Bader  8 ,  Mathis Richter  9 ,  Fengjun Zhang  9 ,  Raphael Chevre  9 ,  Bernd Giebel  4 ,  Stephan Lang  3  10 ,  Anika Grüneboom  2 ,  Daniela Maier-Begandt  8 ,  Anja Hasenberg  1 ,  Oliver Soehnlein  9 ,  Hans Christian Reinhardt  5  11  12 ,  Sven Heiles  2  13 ,  Jianxu Chen  2 ,  Jadwiga Jablonska  3  10 ,  Albert Sickmann  2  14 ,  Dirk M Hermann  6 ,  Matthias Gunzer  1  2
Affiliations
  • 1. Institute For Experimental Immunology and Imaging, University Hospital, University of Duisburg-Essen, Essen, Germany.
  • 2. Leibniz-Institut Für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany.
  • 3. Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
  • 4. Institute For Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • 5. Department of Hematology and Stem Cell Transplantation, West-German Cancer Center, University Hospital Essen, Essen, Germany.
  • 6. Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • 7. Academy for Multidisciplinary Studies, Capital Normal University, Beijing, China.
  • 8. Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Ludwig-Maximilians-Universität München, Munich, Germany.
  • 9. Institute For Experimental Pathology, Centre of Molecular Biology of Inflammation, University of Münster, Münster, Germany.
  • 10. Partner Site Düsseldorf/Essen, German Cancer Consortium (DKTK), Essen, Germany.
  • 11. West German Cancer Center, University Hospital Essen, Essen, Germany.
  • 12. Center For Molecular Biotechnology, University Hospital Essen, Essen, Germany.
  • 13. Faculty of Chemistry, University of Duisburg-Essen, Essen, Germany.
  • 14. Medical Faculty, Ruhr-Universität Bochum, Bochum, Germany.
PMID: 42325214 DOI: 10.1002/advs.76236
Abstract

The surface protein CD177 on human neutrophil granulocytes is linked to tissue infiltration. In most individuals, circulating neutrophils comprise distinct fractions of CD177-expressing (CD177+) and non-expressing (CD177-) cells, which differ functionally and influence disease outcomes. Currently, CD177 is considered a dynamic activation marker ultimately expressed by most neutrophils. Here, we show that, instead, CD177--neutrophils represent a stable subpopulation that never acquires CD177. CD177+- to CD177--neutrophil ratios persist over time in individuals, regardless of circadian rhythms or inflammation. Neutrophils remain CD177- during in vitro stimulation and are morphologically similar to CD177+-cells, but differ markedly regarding protein composition. Following stem cell transplantation, the host bone marrow defines the CD177-pattern of mature neutrophils. Functionally, CD177- neutrophils display pro-tumoral properties, including elevated Arginase expression and enhanced tumor-supporting activity, are enriched in human head-and-neck Cancer tissues, and associated with adverse clinical outcomes. Hence, CD177-expression or -absence defines stable human neutrophil subtypes with distinct functions.

Keywords
CD177; cancer; human neutrophils; inflammation; transmigration.
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