| Title: | The lysosome–cathepsin axis in pancreatic cancer : mechanisms of stromal remodeling, immune evasion, and therapy resistance |
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| Authors: | ID Mazej Jeram, Nika, Institut "Jožef Stefan" (Author)
ID Senjor, Emanuela, Institut "Jožef Stefan" (Author)
ID Kos, Janko, Institut "Jožef Stefan" (Author)
ID Perišić, Milica, Institut "Jožef Stefan" (Author) |
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| Files: |  URL - Source URL, visit https://www.mdpi.com/2218-273X/16/6/824
 PDF - Presentation file, download (1,92 MB)
MD5: 54C99CCCF8787CC4098F81A5B9CB73F9
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| Language: | English |
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| Typology: | 1.02 - Review Article |
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| Organization: |  IJS - Jožef Stefan Institute
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| Abstract: | Pancreatic cancer remains one of the most lethal malignancies worldwide, with pancreatic ductal adenocarcinoma accounting for the vast majority of cases and characterized by extensive desmoplasia, immune exclusion, and resistance to systemic therapies. Increasing evidence implicates lysosomal cathepsins as important regulators of these defining features of pancreatic tumor biology. Cathepsin-dependent proteolysis and lysosome-associated signaling pathways contribute to extracellular matrix remodeling, regulate immune cell trafficking, and influence antigen processing and presentation. Beyond their classical degradative functions, cathepsins participate in stress-adaptive cellular programs linked to autophagy, metabolic regulation, and proteostasis, supporting tumor cell survival under hypoxic, nutrient-limited, and therapy-induced stress conditions. Within the tumor microenvironment, dysregulated cathepsin activity promotes immune evasion by reshaping cytokine networks, impairing effective antigen presentation, and reinforcing physical and functional barriers to cytotoxic T-cell infiltration. Collectively, these mechanisms position the lysosome–cathepsin system as a central regulator of proteolytic remodeling, immune exclusion, and adaptive therapy resistance in pancreatic cancer, highlighting its potential relevance for emerging combinatorial therapeutic strategies. |
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| Keywords: | tumor microenvironment, autophagy, therapeutic resistance, immune evasion, extracellular matrix remodelling, cytotoxic cells, antigen presentation, lysosome |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 22.04.2026 |
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| Article acceptance date: | 27.05.2026 |
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| Publication date: | 02.06.2026 |
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| Publisher: | MDPI |
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| Year of publishing: | 2026 |
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| Number of pages: | str. 1-40 |
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| Numbering: | Vol. 16, iss. 6, [art. no.] 824 |
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| Source: | Švica |
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| PID: | 20.500.12556/DiRROS-29780  |
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| UDC: | 577 |
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| ISSN on article: | 2218-273X |
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| DOI: | 10.3390/biom16060824 |
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| COBISS.SI-ID: | 280443139 |
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| Copyright: | © 2026 by the authors. |
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| Note: | Nasl. z nasl. zaslona;
Soavtorji: Emanuela Senjor, Janko Kos, Milica Perišić Nanut;
Opis vira z dne 4. 6. 2026;
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| Publication date in DiRROS: | 05.06.2026 |
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| Views: | 89 |
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| Downloads: | 67 |
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