The predictive value of tumor infiltrating leukocytes in Hepatocellular Carcinoma: A systematic review and meta-analysis

• Published in: European journal of surgical oncology Vol. 47; no. 10; pp. 2561 - 2570
• Main Authors: Schoenberg, Markus Bo, Li, Xiaokang, Li, Xinyu, Han, Yongsheng, Hao, Jingcheng, Miksch, Rainer Christoph, Koch, Dominik, Börner, Nikolaus, Beger, Nicola Theresa, Bucher, Julian Nikolaus, Schiergens, Tobias Simon, Guba, Markus Otto, Werner, Jens, Bazhin, Alexandr V.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2021
• Subjects: B-Lymphocytes; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; CD3 Complex - metabolism; CD8-Positive T-Lymphocytes; Clinical oncology; Disease-Free Survival; Hepatectomy; Hepatocellular carcinoma; Humans; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Lymphocytes, Tumor-Infiltrating - metabolism; Macrophages; Meta-analysis; Natural Killer T-Cells; Neutrophils; Predictive Value of Tests; Survival Rate; T-Lymphocytes, Regulatory; Tumor infiltrating leukocytes; Tumor infiltrating leukocytes; Hepatocellular carcinoma; Clinical oncology; Hepatectomy; Meta-analysis
• ISSN: 0748-7983; 1532-2157
• DOI: 10.1016/j.ejso.2021.04.042

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).
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.
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.
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.