The Tumor Immune Microenvironment in Pancreatic Ductal Adenocarcinoma: Neither Hot nor Cold

SIMPLE SUMMARY: In this review, we discuss the current understanding of pro- and anticancer immune responses in the tumor immune microenvironment of pancreatic ductal adenocarcinoma. We describe the duality and complexity of immune cell functions in the tumor microenvironment and also illustrate therapeutic approaches that modulate the antitumor immune response. ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic tumor and is associated with poor prognosis and treatment response. The tumor microenvironment (TME) is recognized as an important factor in metastatic progression across cancers. Despite extensive study of the TME in PDAC, the cellular and molecular signaling networks remain poorly understood, largely due to the tremendous heterogeneity across tumors. While earlier work characterized PDAC as an immunologically privileged tumor poorly recognized by the immune system, recent studies revealed the important and nuanced roles of immune cells in the pathogenesis of PDAC. Distinct lymphoid, myeloid, and stromal cell types in the TME exert opposing influences on PDAC tumor trajectory, suggesting a more complex organization than the classical “hot” versus “cold” tumor distinction. We review the pro- and antitumor immune processes found in PDAC and briefly discuss their leverage for the development of novel therapeutic approaches in the field.