Circulating Monocytes Serve as Novel Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma Patients

SIMPLE SUMMARY: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases. The association of monocytes with worse outcomes has been demonstrated for a wide array of malignancies. Yet, their role in PDAC remains to be elucidated. In this study, we found elevated levels of circulating monocytes in PDAC patients, correlating with more aggressive tumor growth and decreased survival. Therefore, we propose that monocytes may act as a novel prognostic biomarker for PDAC. Future large-scale studies are needed to investigate monocytes as potential therapeutic targets. ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) ranks among the most fatal cancer diseases, widely accepted to have the most dismal prognoses. Although immunotherapy has broadly revolutionized cancer treatment, its value in PDAC appears to be relatively low. Exhibiting protumoral effects, monocytes have recently been proposed as potential targets of such immunotherapeutic regimens. However, to date, the body of evidence on monocytes’ role in PDAC is scarce. Therefore, we analyzed monocytes in the peripheral blood of 58 PDAC patients prior to surgery and compared them to healthy individuals. PDAC patients showed increased levels of monocytes when compared to healthy controls In addition, patients with perineural infiltration demonstrated a higher percentage of monocytes compared to non-infiltrating tumors and PDAC G3 was associated with higher monocyte levels than PDAC G2. Patients with monocyte levels > 5% were found to have an 8.9-fold increased risk for a G3 and perineural infiltrated PDAC resulting in poorer survival compared to patients with <5% monocyte levels. Furthermore, PDAC patients showed increased expressions of CD86 and CD11c and decreased expressions of PD-L1 on monocytes compared to healthy individuals. Finally, levels of monocytes correlated positively with concentrations of IL-6 and TNF-α in plasma of PDAC patients. Based on our findings, we propose monocytes as a novel prognostic biomarker. Large-scale studies are needed to further decipher the role of monocytes in PDAC and investigate their potential as therapeutic targets.