20.500.12556/DiRROS-29780 The lysosome–cathepsin axis in pancreatic cancer mechanisms of stromal remodeling, immune evasion, and therapy resistance The lysosome–cathepsin axis in pancreatic cancer: mechanisms of stromal remodeling, immune evasion, and therapy resistance 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. tumor microenvironment autophagy therapeutic resistance immune evasion extracellular matrix remodelling cytotoxic cells antigen presentation lysosome tumorsko mikrookolje avtofagija citotoksične celice lizosom true false true MDPI Švica Angleški jezik Slovenski jezik © 2026 by the authors. Neznano 2026-06-05 09:39:40 2026-06-05 09:39:41 2026-06-06 03:58:31 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Soavtorji: Emanuela Senjor, Janko Kos, Milica Perišić Nanut; Opis vira z dne 4. 6. 2026; str. 1-40 iss. 6, [art. no.] 824 Vol. 16 Jun. 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2026-04-22 2026-05-27 2026-06-02 577 2218-273X 10.3390/biom16060824 280443139 https://www.mdpi.com/2218-273X/16/6/824 1 b7b1f9cc-60b1-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44767 RAZ_Mazej_Jeram_Nika_2026.pdf RAZ_Mazej_Jeram_Nika_2026.pdf 1 54C99CCCF8787CC4098F81A5B9CB73F9 b44e06c1f34c25b7003629091f47eee685ada529cda5b46a889a2f5f86e1ad01 14b2cda9-60b2-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44770 Institut Jožef Stefan 0 0 0