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.
Highlights
The oncogenesis and development of malignant tumors, including initiation, progression, malignant conversion, invasion and metastasis, are dynamic processes that involve multiple links, stages and genes
The results indicated that high levels of CD3+ T lymphocytes were associated with good overall survival (OS) (HR = 0.63; 95% confidence intervals (95% CIs), 0.41–0.94; P = 0.03; Fig. 1C) and disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 0.60; 95% CI, 0.40–0.89; P = 0.01; Fig. 1D)
Some studies assessed the prognostic value of tumor-infiltrating lymphocytes in various types of tumors, such as breast cancer, gastric cancer, non-small cell lung cancer, and ovarian cancer[38,39,40,41]
Summary
The oncogenesis and development of malignant tumors, including initiation, progression, malignant conversion, invasion and metastasis, are dynamic processes that involve multiple links, stages and genes. The immune response has a vital function via regulation of carcinogenesis and cancer progression, including promotion and suppression[5, 6]. Current research has demonstrated that immunotherapy plays a valuable role in anti-tumor treatments, such as active vaccination, adoptive cell transfer therapy and immune checkpoint blockade. Tumor-infiltrating lymphocytes (TILs), as the most important monitor of the immune response, are a focus of cancer research. CD3+, CD4+, CD8+ and FoxP3+ T lymphocytes are the most common subsets of TILs. CD8+ T lymphocytes primarily belong to cytotoxic T lymphocytes (CTLs), which are primarily responsible for the removal of target cells, including tumor cells. We performed a meta-analysis based on data acquired from published studies using specific inclusion and exclusion criteria to clarify the prognostic value of TILs and the ratios of different subsets in HCC. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used as effect measures
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