Abstract
This study aimed to elucidate the prognostic implications of intratumoral and peritumoral infiltrating T-lymphocytes in pancreatic ductal adenocarcinoma (PDAC) through a meta-analysis. A total of 18 eligible studies and 2453 PDAC patients were included in the present study. Intratumoral and peritumoral infiltrating lymphocytes were evaluated using various markers, such as CD3, CD4, CD8, FOXP3, and immune cell score. The correlations between these parameters and overall and disease-free survival were investigated and used in the meta-analysis. High intratumoral infiltration of CD3-, CD4-, and CD8-expressing lymphocytes was significantly correlated with better overall survival (hazard ratio (HR) 0.747, 95% confidence interval (CI) 0.620–0.900, HR 0.755, 95% CI 0.632–0.902, and HR 0.754, 95% CI 0.611–0.930, respectively). However, there was no significant correlation between PDAC prognosis and intratumoral FOXP3 or immune cell score (HR 1.358, 95% CI 1.115–1.655 and HR 0.776, 95% CI 0.566–1.065, respectively). Moreover, there was no significant correlation between the prognosis and peritumoral infiltrating T-lymphocytes. In evaluations of disease-free survival, only high intratumoral CD4 infiltration was correlated with a better prognosis (HR 0.525, 95% CI 0.341–0.810). Our results showed that high intratumoral infiltrating lymphocytes were significantly correlated with a better PDAC prognosis. However, among the tumor-infiltrating lymphocytes, CD3, CD4, and CD8 had prognostic implications, but not FOXP3 and immune cell score.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors [1,2]
The tumor microenvironment, which is important in tumor behavior, comprises various cellular and molecular factors, including tumor-infiltrating lymphocytes (TILs) [5,6,7,8,9,10,11]
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Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors [1,2]. Significant correlations between worse survival and regulatory T cells or myeloid-derived suppressor cells have been reported [5,6,7,8,9,10,11]. These cells involve tumor growth and angiogenesis extension [5,6,7,8,9,10,11]. Detailed information on the prognostic implications of different TILs remain unclear in PDAC. In PDAC immunotherapy research, detailed information on TILs can be more important, and the prognostic implications according to TIL types can differ. We investigated the prognostic impact of TILs in PDACs and performed a subgroup analysis based on TIL subtypes
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