Significance of tumor infiltrating granulocytes and neutrophil extracellular traps in colorectal cancer
BACKGROUND: Neutrophils are the most abundant granulocytes in the tumor microenvironment and exert both pro- and anti-cancer effects. Activated neutrophils can release neutrophil extracellular traps (NETs) that have been proposed to promote tumor progression and metastasis. We aimed to clarify the significance of NETs and granulocytes in colorectal cancer. METHODS: Our study population consisted of three independent colorectal cancer cohorts (N = 1927). We identified NETs showing positivity for citrullinated histone H3 (Cit-H3) and granulocytes expressing CD66b (CEACAM8) with multiplex immunohistochemistry and used digital image analysis and machine learning tools to calculate their densities in tumor samples. Associations between NET and granulocyte densities with clinicopathologic characteristics, tumor-infiltrating immune cells, prognosis, and systemic inflammation markers were examined. RESULTS: < 0.001). CONCLUSION: NETs does not predict survival.
Authors
- Maarit Ahtiainen (ORCID: https://orcid.org/0000-0002-3263-2307)
- Hanna Elomaa (ORCID: https://orcid.org/0000-0002-5378-7703)
- Ville K. Äijälä (ORCID: https://orcid.org/0009-0005-7664-8027)
- Juha Saarnio (ORCID: https://orcid.org/0000-0002-8443-3625)
- Olli Helminen (ORCID: https://orcid.org/0000-0001-9544-6475)
- Tero Rautio (ORCID: https://orcid.org/0000-0003-4441-9412)
- Erkki‐Ville Wirta (ORCID: https://orcid.org/0000-0002-2255-6136)
- Meeri Kastinen (ORCID: https://orcid.org/0009-0007-0954-5612)
- Markus J. Mäkinen (ORCID: https://orcid.org/0000-0002-9200-4118)
- Päivi Sirniö (ORCID: https://orcid.org/0000-0002-3988-3782)
- Vesa‐Matti Pohjanen (ORCID: https://orcid.org/0000-0002-4129-4346)
- Raila Aro (ORCID: https://orcid.org/0000-0001-8193-8460)
- Reetta Häivälä (ORCID: https://orcid.org/0009-0001-4537-1214)
- Henna Karjalainen (ORCID: https://orcid.org/0009-0008-4694-6703)
- Jukka M. J. Rintala (ORCID: https://orcid.org/0000-0003-1865-8444)
- Juha P. Väyrynen (ORCID: https://orcid.org/0000-0002-8683-2996)
- Anne Tuomisto (ORCID: https://orcid.org/0000-0002-9949-1887)
- Vilja V. Tapiainen (ORCID: https://orcid.org/0009-0003-6306-6525)
- Sanna Meriläinen (ORCID: https://orcid.org/0000-0002-5418-4373)
- Akseli Kehusmaa (ORCID: https://orcid.org/0009-0004-9415-7283)
- Aino Ojanperä (ORCID: https://orcid.org/0009-0000-9399-2253)
- Oskari Rahkola (ORCID: https://orcid.org/0009-0004-0865-3302)
- Jukka-Pekka Mecklin
- Toni T. Seppälä
- Jan Böhm
Institutions
- University of Helsinki (FI)
- Oulu University Hospital (FI)
- Helsinki University Hospital (FI)
- Tampere University Hospital (FI)
- Tampere University (FI)
- Central Finland Health Care District (FI)
- University of Jyväskylä (FI)
Publication Details
- Journal
- British Journal of Cancer
- Published
- 2026-04-06
- DOI
- https://doi.org/10.1038/s41416-026-03409-x
- Primary Topic
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Suomen Lääketieteen Säätiö
- Jane ja Aatos Erkon Säätiö
- Emil Aaltosen Säätiö
- Syöpäsäätiö