Pancreatic cancer remains a leading cause of cancer-related mortality worldwide. Tumor-infiltrating lymphocytes (TILs) play an important role in mediating tumor progression and treatment resistance in pancreatic cancer. However, the prognostic value of TILs in pancreatic cancer remains uncertain. This meta-analysis evaluated the prognostic significance of TIL subsets (CD3+, CD4+, CD8+, FoxP3+ T cells) on overall survival (OS) and disease-free survival (DFS) of patients with resected pancreatic ductal adenocarcinoma.
Pertinent studies were gathered through systematic search of PubMed, Google Scholar and Cochrane Library databases up to August 1, 2019. Using Review Manager version 5.3, pooled hazard ratios and 95% confidence intervals were calculated using random or fixed effects models, depending on the heterogeneity of studies.
A total of 11 studies comprising 1760 patients were included. Pooled analysis revealed that high levels of CD8+ TILs were associated with improved OS (HR = 0.59, 95% CI = 0.51-0.69, p < 0.00001) and DFS (HR = 0.60, 95% CI = 0.50-0.73, p < 0.00001). Similarly, high levels of CD3+ TILs correlated with better OS (HR = 0.64, 95% CI = 0.54-0.75, p < 0.00001) and DFS (HR = 0.53, 95% CI = 0.31-0.92, p < 0.0001). In contrast, high FoxP3+ TILs associated with worse OS (HR = 1.37, 95% CI = 1.00-1.87, p = 0.05), with no significant difference in DFS (HR = 1.21, 95% CI = 0.88-1.67, p = 0.23). While high CD4+ TILs showed significant improvement in OS (HR = 0.74, 95% CI = 0.63-0.86, p = 0.0001), there was no significant disparity in DFS (HR = 0.79, 95% CI = 0.47-1.35, p = 0.39).
TILs are a promising prognostic biomarker in pancreatic cancer. High levels of CD8+ TILs correlated with favorable OS and DFS, while high levels of FoxP3+ TILs associated with poor OS. Nonetheless, results of this meta-analysis should be approached with caution due to the lack of established standards in assessment of TILs and the small number of available studies. Prospective studies that assess TILs in a more comprehensive and standardized manner are needed.
Clinical trial identification
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All authors have declared no conflicts of interest.