Clinical Significance of Tumor-Infiltrating Conventional and Plasmacytoid Dendritic Cells in Pancreatic Ductal Adenocarcinoma

SIMPLE SUMMARY: The tumor immune contexture plays a pivotal role for the clinical outcome of cancer patients and the efficacy of various treatment modalities. Dendritic cells (DCs) represent a major component of the tumor immune architecture that can either efficiently promote antitumor immunity or contribute to immunosuppression. Here, we investigated the frequency, spatial organization, and clinical significance of tumor-infiltrating conventional DCs type 1 (cDC1s) and type 2 (cDC2s) and plasmacytoid DCs (pDCs) in pancreatic ductal adenocarcinoma (PDAC). A higher frequency of whole tumor area (WTA)- and tumor stroma (TS)-infiltrating cDC1s, and of intraepithelial tumor-infiltrating cDC2s, was significantly associated with improved survival. Furthermore, a higher density of both WTA- and TS-infiltrating cDC1s and pDCs emerged as an independent prognostic factor for better survival. These results provide evidence that tumor-infiltrating DCs are associated with survival of PDAC patients and may support the design of novel DC-based immunotherapeutic strategies. ABSTRACT: Dendritic cells (DCs) play a key role in the orchestration of antitumor immunity. Activated DCs efficiently enhance antitumor effects mediated by natural killer cells and T lymphocytes. Conversely, tolerogenic DCs essentially contribute to an immunosuppressive tumor microenvironment. Thus, DCs can profoundly influence tumor progression and clinical outcome of tumor patients. To gain novel insights into the role of human DCs in pancreatic ductal adenocarcinoma (PDAC), we explored the frequency, spatial organization, and clinical significance of conventional DCs type 1 (cDC1s) and type 2 (cDC2s) and plasmacytoid DCs (pDCs) in primary PDAC tissues. A higher density of whole tumor area (WTA)- and tumor stroma (TS)-infiltrating cDC1s was significantly associated with better disease-free survival (DFS). In addition, an increased frequency of intraepithelial tumor-infiltrating cDC2s was linked to better DFS and overall survival (OS). Furthermore, an increased density of WTA- and TS-infiltrating pDCs tended to improve DFS. Moreover, a higher frequency of WTA- and TS-infiltrating cDC1s and pDCs emerged as an independent prognostic factor for better DFS and OS. These findings indicate that tumor-infiltrating DCs can significantly influence the clinical outcome of PDAC patients and may contribute to the design of novel treatment options that target PDAC-infiltrating DCs.