| Title: | Tumor immune microenvironment in pancreatic ductal adenocarcinoma revisited - Exploring the "Space" |
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| Authors: | ID Bräutigam, Konstantin (Author)
ID Skok, Kristijan (Author)
ID Szymonski, Krzysztof (Author)
ID Vestrup Rift, Charlotte (Author)
ID Karamitopoulou, Eva (Author) |
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| Files: |  RAZ_Brautigam_Konstantin_2025.pdf (6,62 MB)
MD5: E97BD6D6563AD25BADD93A1C1921240D
 https://doi.org/10.1016/j.canlet.2025.217699
https://www.sciencedirect.com/science/article/pii/S0304383525002654?via%3Dihub
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| Language: | English |
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| Work type: | Scientific work |
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| Typology: | 1.02 - Review Article |
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| Organization: | MF - Faculty of Medicine
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| Abstract: | 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. |
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| Keywords: | immune system, pancreatic adenocarcinoma (PDAC), spatial analysis, tumor immune microenvironment (TIME), tumor infiltrating lymphocytes (TILs) |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 24.03.2025 |
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| Article acceptance date: | 21.12.2024 |
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| Publication date: | 01.07.2025 |
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| Publisher: | Elsevier B. V. |
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| Year of publishing: | 2025 |
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| Number of pages: | Str. [1]-8 |
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| Numbering: | Letn. 622, Št. članka 217699 |
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| PID: | 20.500.12556/DKUM-94293  |
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| UDC: | 616 |
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| ISSN on article: | 1872-7980 |
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| COBISS.SI-ID: | 245415171 |
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| DOI: | 10.1016/j.canlet.2025.217699 |
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| Publication date in DKUM: | 18.08.2025 |
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| Views: | 166 |
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| Downloads: | 10 |
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| Metadata: |    |
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| Categories: | Misc.
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