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. 2021 Mar 19;13(7):9665-9678.
doi: 10.18632/aging.202710. Epub 2021 Mar 19.

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

Fengwei Gao  1 , Kunlin Xie  1 , Qiwen Xiang  2 , Yan Qin  2 , Panyu Chen  2 , Haifeng Wan  1 , Yang Deng  3 , Jiwei Huang  1 , Hong Wu  1
Affiliations

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

Fengwei Gao et al. Aging (Albany NY). .

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.

Keywords: hepatocellular carcinoma; prognosis; tumor-infiltrating lymphocytes.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Prognostic value of TILs in hepatocellular carcinoma. Kaplan-Meier curves of estimated overall survival and disease-free survival in the WCH set (A) and the TCGA set (B). Patients without survival information were excluded from the analysis.
Figure 2
Figure 2
Nomogram predicting survival possibility according to TIL intensity. The values for each prediction factors are marked. From each mark, a vertical line is drawn downward to determine the points, which are subsequently added together and is marked on the Total-points line. Finally, a vertical line is followed downward to the accompanying lines indicating the 1,3 and 5 year survival possibility.
Figure 3
Figure 3
Histopathologic examples of lymphocytic infiltration in hepatocellular carcinoma on H&E-stained tumor sections. Example of tumors with varying intensity of stromal TILs by H&E: (A) 1%, (B) 1%, (C) 5%, (D) 5%, (E) 10%, (F) 20%, (G) 30%, (H) 40%, (I) 50%, (J) 60%, (K) 70%, (L) 80%, and (M) 90%.
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