Tertiary lymphoid structure-associated chemokine programs define an immune-organized tumor microenvironment with prognostic relevance in hepatocellular carcinoma

doi:10.4251/wjgo.126440

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Dec 15, 2026; 18(12): 126440
Published online Dec 15, 2026. doi: 10.4251/wjgo.126440

Tertiary lymphoid structure-associated chemokine programs define an immune-organized tumor microenvironment with prognostic relevance in hepatocellular carcinoma

Kun Chen, Yue-Qi Wang, Meng-Chen Guo, Xiao-Yu Gu, Xue-Mei Chen, Su-Su Luo, Shuang Liu

Kun Chen, Yue-Qi Wang, Xiao-Yu Gu, Xue-Mei Chen, Shuang Liu, Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing 210000, Jiangsu Province, China

Yue-Qi Wang, Shuang Liu, Department of Laboratory Medicine, Medical School of Southeast University, Nanjing 210000, Jiangsu Province, China

Meng-Chen Guo, Center of Clinical Laboratory Medicine, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China

Su-Su Luo, The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China

Su-Su Luo, Moores Cancer Center, School of Medicine, University of California San Diego, San Diego, CA 92093, United States

Author contributions: Chen K and Liu S were responsible for the conception and design of the study; Wang YQ, Luo SS and Chen K were major contributors in writing the original draft; Guo MC, Gu XY and Chen XM were involved in data curation and data analysis; Chen K and Guo MC contributed to project administration and funding. All authors have read and approved the final version of the manuscript.

AI contribution statement: No artificial intelligence (AI) tools were used in the preparation of this manuscript. The authors take full responsibility and accountability for the integrity, accuracy, originality, and scientific validity of the manuscript and all submitted materials.

Supported by Scientific Research Incubation Fund of Jiangbei Campus, Zhongda Hospital, Southeast University, No. 202302Q; and the National Natural Science Foundation of China, No. 32400043.

Conflict-of-interest statement: The authors declare that there are no conflicts of interest.

Corresponding author: Shuang Liu, Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, No. 87 Dingjiaqiao Road, Gulou District, Nanjing 210000, Jiangsu Province, China. liushuang@seu.edu.cn

Received: August 4, 2026
Revised: September 16, 2026
Accepted: October 16, 2026
Published online: December 15, 2026
Processing time: 98 Days and 0.6 Hours

Core Tip

Core Tip: Tertiary lymphoid structures (TLSs) are organized immune aggregates and their transcriptional programs remain poorly defined in hepatocellular carcinoma (HCC). Using multiple public cohorts, we anchored a 12-chemokine TLS signature to histology-annotated TLS status, localized chemokine and receptor expression using single-cell transcriptomic profiling, and derived a seven-gene prognostic score. The score stratified overall survival in a training cohort and an independent validation cohort. This study provides a scalable, histology-anchored transcriptomic framework for immune stratification in HCC.