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Zhao ZW, Chen YG, Wang GY. Mechanisms, clinical translation, and future perspectives of liver-mediated immunoprotection in combined organ transplantation. World J Gastrointest Surg 2026; 18(11): 124378 [DOI: 10.4240/wjgs.124378]
World J Gastrointest Surg. Nov 27, 2026; 18(11): 124378 Published online Nov 27, 2026. doi: 10.4240/wjgs.124378
Mechanisms, clinical translation, and future perspectives of liver-mediated immunoprotection in combined organ transplantation
Zheng-Wei Zhao, Yu-Guo Chen, Guang-Yi Wang
Zheng-Wei Zhao, Yu-Guo Chen, Guang-Yi Wang, Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Co-corresponding authors: Yu-Guo Chen and Guang-Yi Wang.
Author contributions: Chen YG and Wang GY contributed equally to this manuscript and are co-corresponding authors. Zhao ZW and Chen YG wrote and edited the manuscript; Chen YG and Wang GY conceptualized the research topic and submitted the revised manuscript with all the related documents; and all authors thoroughly reviewed and endorsed the final manuscript.
AI contribution statement: Deepseek V3 was used for language polishing and literature review. The figure was generated by Gemini. AI tools were not involved in study design, data collection, or interpretation of results.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Guang-Yi Wang, Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun 130021, Jilin Province, China. guangyi@jlu.edu.cn
Received: June 12, 2026 Revised: July 6, 2026 Accepted: August 31, 2026 Published online: November 27, 2026 Processing time: 152 Days and 19.3 Hours
Abstract
Owing to its unique tolerogenic immune microenvironment, the liver can confer substantial immunologic protection on concurrently transplanted allogeneic grafts in combined organ transplantation. This review summarizes the molecular and cellular mechanisms underlying liver-mediated immunoprotection, including antigen presentation by liver sinusoidal endothelial cells and tolerogenic dendritic cells, enrichment of regulatory T cells, clonal deletion of donor-reactive T cells, clearance of donor-specific antibodies, and the establishment of microchimerism. We further synthesize clinical outcome data from combined liver-intestinal transplantation and multivisceral transplantation, and evaluate the translational potential of optimized immunosuppressive strategies, cell-based therapies, and emerging technologies such as normothermic machine perfusion. Although current evidence supports the immunoprotective role of the liver, its precise molecular mechanisms remain incompletely defined and require further validation. Prospective multicenter studies are also warranted.
Core Tip: This review highlights the immunoprotective mechanisms of the liver in combined intestinal and multivisceral transplantation, including liver sinusoidal endothelial cell-mediated antigen presentation, regulatory T cell enrichment, clonal deletion, and donor-specific antibody clearance. Concurrent liver inclusion reduces rejection rates but increases risks of graft-vs-host disease and infection. Normothermic machine perfusion and regulatory T-cell therapy represent promising strategies for optimizing immunomodulation.
