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

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

World J Gastrointest Surg. 2022 Sep 27;14(9):1008-1025. doi: 10.4240/wjgs.v14.i9.1008.

Authors

Wei Wang^{1

2}, Zhen-Feng Deng^{1

2}, Ji-Long Wang^{1

2}, Ling Zhang³, Li Bao⁴, Bang-Hao Xu^{1

2}, Hai Zhu^{1

2}, Ya Guo^{1

2}, Zhang Wen^{1

5}

Affiliations

¹ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
² 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.
³ Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
⁴ Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300000, China.
⁵ 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. wenzgxmu@163.com.

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; Multiplexed immunohistochemistry; Tumor necrosis; Tumor-infiltrating lymphocytes.