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Research Paper|Volume 13, Issue 7|pp 9665—9678

The density of tumor-infiltrating lymphocytes and prognosis in resectable hepatocellular carcinoma: a two-phase study

Fengwei Gao1, Kunlin Xie1, Qiwen Xiang2, Yan Qin2, Panyu Chen2, Haifeng Wan1, Yang Deng3, Jiwei Huang1, Hong Wu1
  • 1Department of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China
  • 2Operation Room of West China Hospital, West China School of Nursing, Sichuan University, Chengdu, China
  • 3Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
* Equal contribution
Received: July 16, 2020Accepted: February 1, 2021Published: March 19, 2021
https://doi.org/10.18632/aging.202710

Copyright: © 2021 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aim: Previous studies have focused on the subpopulations of tumor-infiltrating lymphocytes (TILs) in tumors. This study focuses only on the concentration of TILs in the tumor irrespective of type and elucidates its prognostic value.

Methods: We used 315 HCC patients as the discovery phase and another 343 HCC patients as the validation phase. By following the standardized guideline, density of TILs were categorized into low (TILs < 10%), intermediate (10% ≦ TILs < 50%), and high (TILs ≧ 50%) levels. Associations of TILs with prognostic, immune-related, and genetic variables were examined.

Results: We observed a dose-response relation of TILs with overall survival (intermediate: HR, 0.58; 95% confidence interval (CI), 0.36-0.93; high: HR, 0.37; 95% CI, 0.15-0.93) and disease-free survival (intermediate: HR, 0.35; 95% CI, 0.22-0.58; high: HR, 0.23; 95% CI, 0.09-0.58). The prognostic value of TILs was validated in the TCGA set. Mutation burden or the number of neoantigens were not associated with TILs intensity. However, hepatitis B or C virus infection patients had higher TILs intensity in the para-tumor tissue.

Conclusions: The TILs intensity was associated with patients' survival. If confirmed, this would suggest that clinical routine assessment of TILs could provide prognostic information in HCC.