Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Sep 27, 2022; 14(9): 1008-1025
Published online Sep 27, 2022. doi: 10.4240/wjgs.v14.i9.1008
Change of tumor-infiltrating lymphocyte of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma
Wei Wang, Zhen-Feng Deng, Ji-Long Wang, Ling Zhang, Li Bao, Bang-Hao Xu, Hai Zhu, Ya Guo, Zhang Wen
Wei Wang, Zhen-Feng Deng, Ji-Long Wang, Bang-Hao Xu, Hai Zhu, Ya Guo, Zhang Wen, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Wei Wang, Zhen-Feng Deng, Ji-Long Wang, Bang-Hao Xu, Hai Zhu, Ya Guo, Zhang Wen, Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Ling Zhang, Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Li Bao, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300000, China
Author contributions: Wang W and Deng ZF contributed equally to this work; Wang W, Deng ZF, Wang JL, Xu BH, Zhu H, Guo Y, and Wen Z designed the research study; Wang W, Deng ZF, Wang JL, Bao L, and Zhang L performed the research; Bao L, Zhang L, Xu BH, Zhu H, Guo Y, and Wen Z contributed reagents and analytic tools; Wang W, Deng ZF, and Wen Z analyzed the data; Wang W and Deng ZF wrote the manuscript; and all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 8190111624; Guangxi Natural Science Foundation of China, No. 2018JJB140382; Guangxi University Young and Middle-Aged Teachers’ Basic Scientific Research Ability Improvement Project, No. 2019KY0123.
Institutional review board statement: The studies involving human participants were reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data presented in this study are available upon request to the corresponding author.
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared and revised according to the STROBE Statement checklist of items.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhang Wen, MD, PhD, Chief Doctor, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. wenzgxmu@163.com
Received: January 20, 2022
Peer-review started: January 20, 2022
First decision: April 10, 2022
Revised: April 22, 2022
Accepted: August 24, 2022
Article in press: August 24, 2022
Published online: September 27, 2022
Processing time: 245 Days and 1.8 Hours
ARTICLE HIGHLIGHTS
Research background

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is an innovative approach to hepatectomy. The surgical trauma experienced by ALPPS is relatively high. In addition, stage-I ALPPS separates the right and left liver lobes and ligates the right hepatic vein, which causes inflammatory reactions, hypoxia, and tumor necrosis, resulting in a unique and complex immune microenvironment for tumor cells.

Research motivation

The trends and effects of tumor-infiltrating lymphocytes (TIL) residing or recruited in the tumor microenvironment (TME) are still unexplored in studies on ALPPS for hepatocellular carcinoma (HCC).

Research objectives

From an immunological perspective, the immunological effects exerted by the unique TME formed during the treatment of HCC by ALPPS, such as anti-tumor effects or tumor-induced immunosuppression, were investigated to further evaluate the safety and efficacy of ALPPS in treating massive HCC and conduct an in-depth study of TILs in the TME.

Research methods

Patients of the ALPPS and hemi-hepatectomy groups were screened using propensity score matching. Immunofluorescence staining was performed to detect and quantify TILs in tumors and adjacent tissues in these two groups of patients. Trends in TILs in peripheral blood during the perioperative period were compared between the two groups.

Research results

The proportion of tumor necrosis volume at postoperative day 7 after stage-I ALPPS was significantly higher than the pre-operative value (P = 0.024). The proportion of tumor necrosis volume was significantly higher in the high CD8+ T-cell infiltrated group than in the low group before surgery for stage-I ALPPS (P = 0.048).

Research conclusions

From an immunological point of view, ALPPS is safe and feasible for treating right lobe massive HCC. The level of TIL infiltration during the perioperative period is dynamically balanced, and the ALPPS procedure itself does not lead to severe immunosuppression due to reduced TIL infiltration and pathological changes in peripheral blood immune components.

Research perspectives

Many studies on TIL therapy for tumors have entered clinical trials. As an important branch of tumor immunotherapy, TIL therapy is one of the potential directions for the future development of medicine.