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Abstract Details
The predictive value of tumor infiltrating leukocytes in Hepatocellular Carcinoma: A systematic review and meta-analysis
Eur J Surg Oncol. 2021 May 4;S0748-7983(21)00473-X. doi: 10.1016/j.ejso.2021.04.042.Online ahead of print.
Markus Bo Schoenberg1, Xiaokang Li2, Xinyu Li2, Yongsheng Han2, Jingcheng Hao3, Rainer Christoph Miksch2, Dominik Koch2, Nikolaus Börner2, Nicola Theresa Beger2, Julian Nikolaus Bucher2, Tobias Simon Schiergens2, Markus Otto Guba2, Jens Werner1, Alexandr V Bazhin4
Author information
1Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.
2Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany.
3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, PR China.
4Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. Electronic address: Alexandr.Bazhin@med.uni-muenchen.de.
Abstract
Background: For Hepatocellular carcinoma (HCC) surgery either through resection or transplantation often provides the only chance for cure. Since hepatocarcinogenesis and postsurgical prognosis is not only dependent on cirrhosis but also on immune activation and exhaustion, many studies have investigated tumor infiltrating leukocyte (TIL) subsets. This systematic review and meta-analysis aims at describing the cell groups and their predictive power regarding overall (OS), disease free (DFS) and recurrence free survival (RFS).
Material and methods: A systematic search of the PubMed database was conducted (PROSPERO 172324). Data on CD3+, CD8+, Treg, B cells, macrophages, neutrophil and NK-cells were collected from Pubmed and related references up to December 2018. Overall (OS), disease-free (DFS) and recurrence free survival (RFS) in dependence of high vs. low infiltration rates were compared using a random effects meta-analysis.
Results: Altogether data from 3541 patients enrolled in 20 publications were included. Except for Tregs and Neutrophils, heterogeneity analysis was found to be moderate to high across the studies. High CD3+, CD8+, NK-cell infiltration predicted better survival (OS, DFS and RFS; p < 0.05). Higher Treg and Neutrophil infiltration predicted lower OS and DFS. For Macrophages and B cells no difference in survival could be found.
Discussion: As with other solid tumors immune infiltration has a great influence on survival after resection. However, a considerable publication bias cannot be ruled out in mostly retrospective analyses. Nevertheless, in light of novel immune modulatory treatments this opens a new avenue towards effective and well-tolerated adjuvant treatment.