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
Abstract
BACKGROUND

The role of tumor-infiltrating lymphocytes (TILs) in the growth and progression of hepatocellular carcinoma (HCC) has attracted widespread attention.

AIM

To evaluate the feasibility of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for massive HCC by exploring the role of TIL in the tumor microenvironment.

METHODS

Fifteen massive HCC patients who underwent ALPPS treatment and 46 who underwent hemi-hepatectomy were selected for this study. Propensity score matching was utilized to match patients in ALPPS and hemi-hepatectomy groups (1:1). Quantitative analysis of TILs in tumor and adjacent tissues between the two groups was performed by immunofluorescence staining and further analyses with oncological characteristics. In the meantime, trends of TILs in peripheral blood were compared between the two groups during the perioperative period.

RESULTS

Continuous measurement of tumor volume and necrosis volume showed that the proportion of tumor necrosis volume on the seventh day after stage-I ALPPS was significantly higher than the pre-operative value (P = 0.024). In the preoperative period of stage-I ALPPS, the proportion of tumor necrosis volume in the high CD8+ T cell infiltration group was significantly higher than that in the low group (P = 0.048).

CONCLUSION

TIL infiltration level maintained a dynamic balance during the preoperative period of ALPPS. Compared with right hemi-hepatectomy, the ALPPS procedure does not cause severe immunosuppression with the decrease in TIL infiltration and pathological changes in immune components of peripheral blood. Our results suggested that ALPPS is safe and feasible for treating massive HCC from the perspective of immunology. In addition, high CD8+ T cell infiltration is associated with increasing tumor necrosis in the perioperative period of ALPPS.

Keywords: Associating liver partition and portal vein ligation for staged hepatectomy, Tumor-infiltrating lymphocytes, Multiplexed immunohistochemistry, Tumor necrosis

Core Tip: This study was conducted to evaluate the feasibility of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for massive hepatocellular carcinoma by exploring the role of tumor-infiltrating lymphocyte (TIL) subpopulations in the tumor microenvironment. The ALPPS procedure did not cause severe immunosuppression due to reduced TIL infiltration and pathological alterations in peripheral blood immune components. In addition, high perioperative CD8+ T cell infiltration with ALPPS was associated with increased tumor necrosis.