Publication Name	World Journal of Gastroenterology
Manuscript ID	113325
Country	China

Category	Oncology
Manuscript Type	Basic Study
Article Title	Icariin inhibits tumor-associated neutrophil recruitment via the CXCL8-CXCR2 axis and restrains pro-metastatic programs in colorectal cancer
Manuscript Source	Unsolicited Manuscript
All Author List	Yan-Hua Zhao, Juan Chen, Tao Gong, Hai-Yan Ge and Min Li
Funding Agency and Grant Number
Corresponding Author	Min Li, PhD, Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 157 Daming Road, Nanjing 210022, Jiangsu Province, China. limin_2024@163.com
Key Words	Icariin; Neutrophils; Recruitment; C-X-C motif chemokine ligand 8-C-X-C motif chemokine receptor 2 axis; Colorectal cancer; Pro-metastatic program; Progression
Core Tip	This study elucidates a novel mechanism by which the natural compound icariin (ICA) combats colorectal cancer. We demonstrate that ICA upregulates the tumor suppressor SMAD4, thereby inhibiting the production of C-X-C motif chemokine ligand 8 (CXCL8) and other C-X-C motif chemokine receptor 2 (CXCR2)-associated chemokines. This action predominantly limits the recruitment of tumor-associated neutrophils (TANs) via the CXCL8-CXCR2 axis. Notably, ICA not only reduces neutrophil infiltration but also reprograms TANs toward an antitumor N1 phenotype. By disrupting this SMAD4-CXCL8-CXCR2-TAN axis, ICA effectively restrains epithelial-mesenchymal transition and other pro-metastatic processes, positioning it as a promising therapeutic candidate with a distinct immunomodulatory strategy against colorectal cancer progression.
Citation	Zhao YH, Chen J, Gong T, Ge HY, Li M. Icariin inhibits tumor-associated neutrophil recruitment via the CXCL8-CXCR2 axis and restrains pro-metastatic programs in colorectal cancer. World J Gastroenterol 2026; In press

Received	2025-09-23 09:00
Peer-Review Started	2025-09-23 09:00
First Decision by Editorial Office Director	2025-10-17 06:19
Return for Revision	2025-10-17 06:19
Revised	2025-11-16 07:43
Publication Fee Transferred	2025-11-28 05:50
Second Decision by Editor	2026-01-08 02:38
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-01-08 09:37
Articles in Press	2026-01-08 09:37
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1007-9327 (print) and 2219-2840 (online)
Open Access	This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
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