Role of Immune Microenvironment in Pancreatic Ductal Adenocarcinoma: Could It Be Considered a Predictor of Prognosis?

• Published in: Current Oncology
• Main Authors: Ottavia De Simoni, Luca Dal Santo, Marco Scarpa, Giada Munari, Ylenia Camilla Spolverato, Antonio Scapinello, Sara Lonardi, Caterina Soldà, Francesca Bergamo, Alberto Fantin, Romeo Bardini, Pierluigi Pilati, Matteo Fassan, Mario Gruppo
• Format: Article
• Language: English
• Published: MDPI AG 2023-06-01
• Subjects: pancreatic cancer; tumor microenvironment; pancreatic surgery; pancreatectomy; overall survival
• Online Access: https://www.mdpi.com/1718-7729/30/6/417
• ISSN: 1198-0052; 1718-7729

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME). The aim of this study is to determine the potential significant TME immune markers of long-term survival. Methods: We retrospectively included patients with a diagnosis of resectable PDAC having undergone upfront surgery. Immunohistochemical (IHC) staining using tissue microarray for PD-L1, CD3, CD4, CD8, FOXP3, CD20, iNOS and CD163 was performed in order to characterize the TME. The primary endpoint was long-term survival, defined as the Overall Survival > 24 months from surgery. Results: A total of 38 consecutive patients were included, and 14 (36%) of them were long-term survivors. Long-term survivors showed a higher density of CD8+ lymphocytes intra- and peri-acinar (<i>p</i> = 0.08), and a higher CD8/FOXP3 intra- and peri-tumoral ratio (<i>p</i> = 0.05). A low density of intra- and peri-tumoral FOXP3 infiltration is a good predictor of long-term survival (<i>p</i> = 0.04). A significant association of the low density of intra- and peri-tumoral tumor-associated macrophages (TAMs) iNOS+ with long-term survival was detected (<i>p</i> = 0.04). Conclusions: Despite the retrospective nature and small sample size, our study showed that the high infiltration of CD8+ lymphocytes and low infiltration of FOXP3+ and TAMs iNOS+ are predictors of good prognosis. A preoperative assessment of these potential immune markers could be useful and determinant in the staging process and in PDAC management.