Eosinophils and bioactive lipid mediators regulate skin inflammation and cancer growth
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, with local immunity playing a key role in regulating outcome. Nonresolving inflammation has been suggested to drive cancer growth; however, a fundamental understanding of the tumor immune microenvironment in cSCC is still lacking. In this study, we demonstrate tissue-associated tumor eosinophilia in both human and murine cSCC and show that eosinophils promote epithelial hyperplasia and tumor outgrowth. The skin eosinophils display tissue adaptation and dynamically alter their transcriptome according to the microenvironment. Furthermore, we show that the skin bioactive lipidome is significantly altered during inflammation and in cSCC and that this is regulated by eosinophils. Inflamed skin and cSCC tissue are dominated by lipid mediators synthesized by lipoxygenase enzymes, and our results suggest that eosinophils influence the balance between proinflammatory and proresolving lipid mediators. We demonstrate that lipid mediators can regulate epithelial cell expansion, with PCTR1 reducing inflammation-driven growth of tumor cells and eosinophil-driven eoxin C4 blocking this effect. Together, these findings highlight that eosinophils and specific bioactive lipid mediators play important roles in skin biology and carcinogenesis and point to potential previously unreported strategies for treatment of inflammatory disorders and epithelial malignancies.
Date Issued
2025-12-01
Date Acceptance
2025-04-08
Citation
Journal of Investigative Dermatology, 2025, 145 (12), pp.3064-3078.E7
ISSN
0022-202X
Publisher
Elsevier
Start Page
3064
End Page
3078.E7
Journal / Book Title
Journal of Investigative Dermatology
Volume
145
Issue
12
Copyright Statement
© 2025 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
10.1016/j.jid.2025.04.015
Subjects
Bioactive lipid mediators, Cancer, Eosinophils, Inflammation, Skin COX, cyclooxygenase
cSCC, cutaneous squamous cell carcinoma
DMBA, 7,12-dimethylbenz[a]anthracene
EC, epithelial cell
iSkin, inflamed skin
LOX, lipoxygenase
nSkin, naive skin
TME, tumor microenvironment
TPA, 12-O-tetradecanoylphorbol-13-acetate
WT, wild-type
Publication Status
Published
Date Publish Online
2025-05-02