Publication Name	World Journal of Gastrointestinal Oncology
Manuscript ID	121633
Country	China

Category	Gastroenterology & Hepatology
Manuscript Type	Correspondence
Article Title	Letter to the Editor: Spinal IL-33/ST2 blockade for gallbladder carcinoma pain - balancing central analgesia with systemic tumor immune microenvironment risks
Manuscript Source	Unsolicited Manuscript
All Author List	Yi Lu, Xin-Lei Zhou and Fan Chen
Funding Agency and Grant Number
Corresponding Author	Fan Chen, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Zhejiang Provincial Hospital of Chinese Medicine, No. 548 Binwen Road, Binjiang District, Hangzhou 310006, Zhejiang Province, China. chenfan@zcmu.edu.cn
Key Words	Gallbladder carcinoma; Visceral cancer pain; Interleukin-33/suppression of tumorigenicity 2 signaling pathway; Tumor immune microenvironment; Systemic administration; Translational medicine; Intrathecal delivery; Neuroinflammation
Core Tip	This article highlights a critical translational blind spot in targeting the spinal interleukin-33/suppression of tumorigenicity 2 axis for gallbladder carcinoma-induced pain. While local blockade exhibits analgesic efficacy, systemic administration risks impairing CD8+ T cell-mediated intrinsic anti-tumor immunity - a critical risk fundamentally masked by the original study’s use of athymic nude mice. Furthermore, potential tumor-intrinsic suppression of tumorigenicity 2 activation and stromal remodeling necessitate extreme caution. We strongly advocate that future evaluations utilize immunocompetent syngeneic models to compare intrathecal vs systemic delivery, aiming to safely bridge the gap between analgesic mechanisms and the tumor immune microenvironment.
Citation	Lu Y, Zhou XL, Chen F. Letter to the Editor: Spinal IL-33/ST2 blockade for gallbladder carcinoma pain - balancing central analgesia with systemic tumor immune microenvironment risks. World J Gastrointest Oncol 2026; In press

Received	2026-03-30 03:51
Peer-Review Started	2026-03-31 06:43
First Decision by Editorial Office Director	2026-04-15 07:47
Return for Revision	2026-04-15 07:47
Revised	2026-04-17 17:00
Publication Fee Transferred
Second Decision by Editor	2026-05-19 02:40
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-05-19 06:37
Articles in Press	2026-05-19 06:37
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-5204 (online)
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