Journal article
Potentiating the effect of immunotherapy in pancreatic cancer using gas-entrapping materials
Biomaterials, Vol.317, 123097
06/2025
DOI: 10.1016/j.biomaterials.2025.123097
PMCID: PMC11788032
PMID: 39799699
Abstract
Immune checkpoint inhibitors (ICIs) show limited success in treating pancreatic ductal adenocarcinoma (PDAC), largely due to immune evasion mechanisms, including downregulating expression of major histocompatibility complex class I (MHC-I). Our retrospective analysis demonstrated that smoking – a state of elevated CO exposure – is correlated with increased MHC I expression in pancreatic tumors. Here we tested our hypothesis that introducing exogenous CO augments the anti-cancer effects of immunotherapy. To evaluate this influence, we created a novel oral delivery system for CO, termed CO-Gas-entrapping materials (GeMs), utilizing Food and Drug Administration Generally Recognized as Safe components. In vitro studies demonstrated that CO exposure increased MHC-I and PD-L1 gene and protein expression in various pancreatic cancer cell lines, as well as enhancing T-cell migration and recruitment. In vivo studies showed increased T-cell infiltration in PDAC allograft tumors treated with the combination therapy as confirmed by flow cytometry and immunohistochemical analysis. Further, CO-GeMs combined with ICIs significantly suppressed tumor growth in multiple PDAC mouse models, including subcutaneous and hepatic metastatic allograft models. These findings suggest that CO enhances immune recognition to potentiate the efficacy of ICIs in PDAC. Thus, our CO-GeMs offer a safe, effective method for systemic CO delivery to treat cancer, representing a promising adjunct to immunotherapy in PDAC and potentially other malignancies.
Details
- Title: Subtitle
- Potentiating the effect of immunotherapy in pancreatic cancer using gas-entrapping materials
- Creators
- Megan K. McGovern - University of IowaArielle B. Cafi - University of IowaSri Naga Swetha Tunuguntla - Department of Biomedical Engineering, University of Iowa, Iowa City, IA, 52242, USAAlicia T. Cotoia - University of North Carolina WilmingtonJuan Antonio Raygoza Garay - University of IowaKyle R. Balk - University of IowaLilly Boge - University of IowaSamual Hatfield - University of IowaRyan Courtney - University of IowaJuan Du - University of IowaCarlos H.F. Chan - University of IowaYi Huang - University of IowaVanessa A. Voltarelli - Beth Israel Deaconess Medical CenterMatthew G. Smith - University of IowaAdam Mailloux - University of IowaDustin E. Bosch - University of IowaMichael S. Tift - University of North Carolina WilmingtonLeo E. Otterbein - Beth Israel Deaconess Medical CenterJianling Bi - University of IowaGiovanni Traverso - Massachusetts Institute of TechnologyJames D. Byrne - University of IowaEmily Witt - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Biomaterials, Vol.317, 123097
- DOI
- 10.1016/j.biomaterials.2025.123097
- PMID
- 39799699
- PMCID
- PMC11788032
- NLM abbreviation
- Biomaterials
- ISSN
- 0142-9612
- eISSN
- 1878-5905
- Publisher
- Elsevier Ltd
- Grant note
- University of Iowa Hospitals and Clinics Department of Radiation OncologyHolden Comprehensive Cancer Center at The University of IowaNational Cancer Institute (NCI): K08CA276908 NIH: DP2CA301081 American Cancer Society: IRG-21-141-46 Prostate Cancer Foundation Young Investigator AwardDepartment of Defense Prostate Cancer Program Early Investigator AwardDepartment of Defense Prostate Cancer Program Early Investigator AwardDepartment of DefenseNCINational Football League Players AssociationKarl van Tassel (1925) Career Development ProfessorshipNational Science FoundationMassachusetts Institute of Technology Department of Mechanical Engineering: L30CA274783
We thank the team at SayoStudio for their illustration in Fig. 2. The authors also thank the staff of the University of Iowa Central Microscopy Research Facility for their rapid and detailed work on the histology re-ported in this study. The authors would also like to thank the Holden Comprehensive Cancer Center's Biospecimen Procurement and Molecular Epidemiology Resource (BioMER) for their incredible work identifying, collecting, and sectioning patient samples. This work was funded in part by grants from the University of Iowa Hospitals and Clinics Department of Radiation Oncology, the Holden Comprehensive Cancer Center at The University of Iowa and its National Cancer Institute (NCI) Award P30CA086862 (JDB) , NCI K08CA276908 (JDB) , NIH DP2CA301081 (JDB) , American Cancer Society IRG-21-141-46 (JDB) , Prostate Cancer Foundation Young Investigator Award (JDB) , Department of Defense Prostate Cancer Program Early Investigator Award (JDB) , Department of Defense W81XWH-16-0464 (LEO) , National Football League Players Association (LEO) , National Science Foundation 1927616 (MST) , NCI L30CA274783 (TJB) , Karl van Tassel (1925) Career Development Professorship (GT) and the Massachusetts Institute of Technology Department of Mechanical Engineering (GT) .
- Language
- English
- Date published
- 06/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology; Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Surgery; Radiation Oncology; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984773417902771
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