Abstract
Therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC) can be attributed, in part, to a dense extracellular matrix containing excessive collagen deposition. Here, we describe a novel Salmonella typhimurium (ST) vector expressing the bacterial collagenase Streptomyces omiyaensis trypsin (SOT), a serine protease known to hydrolyze collagens I and IV, which are predominantly found in PDAC. Utilizing aggressive models of PDAC, we show that ST-SOT selectively degrades intratumoral collagen leading to decreases in immunosuppressive subsets, tumor proliferation and viability. Ultimately, we found that ST-SOT treatment significantly modifies the intratumoral immune landscape to generate a microenvironment that may be more conducive to immunotherapy.
Original language | English (US) |
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Article number | 3565 |
Journal | Cancers |
Volume | 13 |
Issue number | 14 |
DOIs | |
State | Published - Jul 2 2021 |
Bibliographical note
Publisher Copyright:© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords
- Attenuated Salmonella typhimurium
- Collagen
- Collagenase
- Desmoplasia
- Pancreatic ductal adenocarcinoma
- Targeted therapies
- Therapeutic resistance
- Tumor microenvironment