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Meta-Analysis
. 2017 Aug 8;7(1):7525.
doi: 10.1038/s41598-017-08128-1.

The Prognostic Value of Tumor-infiltrating Lymphocytes in Hepatocellular Carcinoma: a Systematic Review and Meta-analysis

Wei Yao  1 , Jun-Chuang He  2 , Yan Yang  3 , Jian-Ming Wang  4 , Ya-Wei Qian  1 , Tao Yang  1 , Lei Ji  1
Affiliations
Meta-Analysis

The Prognostic Value of Tumor-infiltrating Lymphocytes in Hepatocellular Carcinoma: a Systematic Review and Meta-analysis

Wei Yao et al. Sci Rep. .

Abstract

Previous clinical studies have found that the levels of tumor-infiltrating lymphocytes (TILs) significantly correlated with prognosis in hepatocellular carcinoma (HCC). However, these conclusions and data remain controversial. We performed a systematic review and meta-analysis to assess the prognostic value and clinical utilization of TILs in patients with HCC. A total of 23 relevant studies of 3173 patients were included into our meta-analysis. The results demonstrated that high levels of CD8 + and CD3 + TILs had a better prognostic value on overall survival (OS), with HRs of 0.71 (P = 0.04) and 0.63 (P = 0.03), respectively, compared to low levels, as did high levels of CD8 + , CD3 + and CD4 + TILs on disease/recurrence-free survival (DFS/RFS), with HRs of 0.66 (P = 0.01), 0.60 (P = 0.01) and 0.79 (P = 0.04), respectively. In contrast, high levels of FoxP3 + TILs had a worse prognostic value on OS and DFS/RFS, with HRs of 2.06 (P < 0.00001) and 1.77 (P < 0.00001), respectively. The FoxP3+/CD4+ and FoxP3+/CD8+ ratios negatively correlated with OS and DFS/RFS. These findings suggest that TILs may serve as a prognostic biomarker in HCC. However, further research should be performed to clarify the clinical value of TILs in HCC.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Forest plots of relationships between levels of CD8+ and CD3+ T lymphocytes and survival. (A) The effect of CD8+ T lymphocytes on OS. (B) The effect of CD8+ T lymphocytes on DFS/RFS. (C) The effect of CD3+ T lymphocytes on OS. (D) The effect of CD3+ T lymphocytes on DFS/RFS.
Figure 2
Figure 2
Forest plots of relationships between levels of CD4+ and Foxp3+ T lymphocytes and survival. (A) The effect of CD3+ T lymphocytes on OS. (B) The effect of CD3+ T lymphocytes on DFS/RFS. (C) The effect of Foxp3+ T lymphocytes on OS. (D) The effect of Foxp3+ T lymphocytes on DFS/RFS. (E) The effect of Foxp3+ T lymphocytes on CSS/CRS.
Figure 3
Figure 3
Forest plots of relationships between the Foxp3+/CD4+ ratio, Foxp3+/CD8+ ratio, CD8+/CD3+ ratio and survival. (A) The effect of the Foxp3+/CD4+ ratio on OS. (B) The effect of the Foxp3+/CD4+ ratio on DFS/RFS. (C) The effect of the Foxp3+/CD8+ ratio on OS. (D) The effect of the Foxp3+/CD8+ ratio on DFS/RFS. (E) The effect of the CD8+/CD3+ ratio on OS. (F) The effect of the CD8+/CD3+ ratio on DFS/RFS.
Figure 4
Figure 4
Funnel plots, Begg’s and Egger’s tests of the meta-analyses assessing the associations between TILs cells and survival. (A) Studies on the effect of CD8+ T cells on OS. (B) Studies on the effect of CD8+ T cells on DFS/RFS. (C) Studies on the effect of Foxp3+ T cells on OS. (D) Studies on the effect of Foxp3+ T cells on DFS/RFS.
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