Prognostic value of tumor-infiltrating lymphocytes, tumor associated neutrophils and metabolic checkpoint molecules on survival of patients with metastatic pancreatic ductal adenocarcinoma.

OBJECTIVES: This study aimed to investigate the tumor microenvironment (TME) of metastatic PDAC, focusing on tumor-infiltrating leukocytes (TILs) and metabolic checkpoint molecules (MCMs). BACKGROUND: The role of TME in primary and metastatic PDAC is not well understood. Furthermore, the role of energy metabolism in metastatic PDAC is unclear. Therefore, this study aimed to explore the TME in primary tumors and metastases of PDAC, and its prognostic role. MATERIALS AND METHODS: We included 26 cases of metastatic PDAC in this study. We performed immunohistochemistry for TILs and MCMs (HIF-1α, GLUT1, and PDHK1) in primary and corresponding metastatic tumor tissues. We quantified stromal TILs and MCMs using a tumor immune stroma (QTiS) algorithm and correlated the data with clinical outcome. RESULTS: We found that CD3(+), CD8(+), and CD20(+) TILs were increased in primary tumors compared to metastatic ones. Kaplan-Meier plots revealed that high infiltration of CD20(+) and its combinations in primary tumors correlated with better OS in metastatic PDAC patients. We also found that high infiltration of CD8(+) TILs in metastatic tumors correlated with better OS, as did the low density of GLUT1 in both PDAC primary and metastatic tumors. A multivariate Cox regression analysis revealed that CD8(+) TILs in metastatic tumors and GLUT1 in PDAC primary and metastatic tumors were independent predictors of survival. CONCLUSION: Distribution of TILs in the TMEs of primary and metastases of metastatic PDAC is different. Our results suggest that TILs (CD8(+)) and MCMs (GLUT1) in tumor stromal areas can predict OS of patients with metastatic PDAC.