20.500.12556/DKUM-94293 Tumor immune microenvironment in pancreatic ductal adenocarcinoma revisited - Exploring the "Space" Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly malignancies with a highly immunosuppressive tumor immune microenvironment (TIME) that hinders effective therapy. PDAC is characterized by significant heterogeneity in immune cell composition, spatial distribution and activation states, which impacts tumor progression and treatment response. Tumour-infiltrating lymphocytes (TILs), including CD4+ T-helper cells, CD8+ cytotoxic T-cells and FOXP3+ regulatory T-cells, play a key role in immune regulation, yet PDAC is largely an immunologically "cold" tumour with limited effector T-cell infiltration. The surrounding cellular microenvironment, particularly Cancer Associated Fibroblasts (CAFs) and macrophages, contributes to immune evasion by promoting a fibrotic and desmoplastic barrier that limits TIL infiltration. The prognostic significance of TILs is increasingly recognized, with higher densities correlating with improved survival, whereas regulatory T-cell infiltration and immunosuppressive stromal interactions are associated with poor outcomes. Emerging therapeutic strategies targeting the TIME (e.g., CAFs), immune checkpoint inhibitors, and TIL-based therapies offer the potential to overcome resistance. Future research must focus on optimizing immunotherapy strategies and unravelling the complex stromal-immune interactions to improve clinical translation. immune system pancreatic adenocarcinoma (PDAC) spatial analysis tumor immune microenvironment (TIME) tumor infiltrating lymphocytes (TILs) true true true Elsevier B. V. Angleški jezik Angleški jezik Znanstveno delo 2025-08-13 03:12:40 2025-08-18 09:56:47 2025-08-19 03:19:51 0000-00-00 00:00:00 2025 0 0 Str. [1]-8 Št. članka 217699 Letn. 622 July 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2025-03-24 2024-12-21 2025-07-01 616 245415171 10.1016/j.canlet.2025.217699 1872-7980 RAZ_Brautigam_Konstantin_2025.pdf RAZ_Brautigam_Konstantin_2025.pdf 1 E97BD6D6563AD25BADD93A1C1921240D 6729ac339ea646e989a68b296d3ef1f8070fbe7a5a2e149acb4e216d74f1bb8f 9ca226fc-7c08-11f0-b405-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=195424 https://doi.org/10.1016/j.canlet.2025.217699 0 c4dba760-7c08-11f0-b405-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=195425 https://www.sciencedirect.com/science/article/pii/S0304383525002654?via%3Dihub 1 9c15b0dd-77e2-11f0-a457-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=195179 Medicinska fakulteta 0 0 0