Captopril, a Renin–Angiotensin System Inhibitor, Attenuates Tumour Progression in the Regenerating Liver Following Partial Hepatectomy
Loading...
Citations
Altmetric:
Altmetric::
Download
Associated Records
File Licence
Editors
Date
2022-05-01
Source Title
International Journal of Molecular Sciences
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Affiliation
Microbiology and Immunology
Surgery (Austin & Northern Health)
Infectious Diseases
Surgery (Austin & Northern Health)
Infectious Diseases
Document Type
Journal Article
Subject Code
Citation
Riddiough, G. E., Walsh, K. A., Fifis, T., Kastrappis, G., Tran, B. M., Vincan, E., Muralidharan, V., Christophi, C., Gordon, C. L. & Perini, M. V. (2022). Captopril, a Renin–Angiotensin System Inhibitor, Attenuates Tumour Progression in the Regenerating Liver Following Partial Hepatectomy. International Journal of Molecular Sciences, 23 (9), https://doi.org/10.3390/ijms23095281.
Access Status
Open Access
Access URL
Open Access URL
Open Access at PMC
Linked Resource URL
NHMRC Grant Code
ARC Grant Code
Description
Abstract
(1) Liver regeneration following partial hepatectomy for colorectal liver metastasis (CRLM) has been linked to tumour recurrence. Inhibition of the renin−angiotensin system (RASi) attenuates CRLM growth in the non-regenerating liver. This study investigates whether RASi exerts an antitumour effect within the regenerating liver following partial hepatectomy for CRLM and examines RASi-induced changes in the tumour immune microenvironment; (2) CRLM in mice was induced via intrasplenic injection of mouse colorectal tumour cells, followed by splenectomy on Day 0. Mice were treated with RASi captopril (250 mg/kg/day), or saline (control) from Day 4 to Day 16 (endpoint) and underwent 70% partial hepatectomy on Day 7. Liver and tumour samples were characterised by flow cytometry and immunofluorescence; (3) captopril treatment reduced tumour burden in mice following partial hepatectomy (p < 0.01). Captopril treatment reduced populations of myeloid-derived suppressor cells (MDSCs) (CD11b+Ly6CHi p < 0.05, CD11b+Ly6CLo p < 0.01) and increased PD-1 expression on infiltrating hepatic tissue-resident memory (TRM)-like CD8+ (p < 0.001) and double-negative (CD4-CD8-; p < 0.001) T cells; (4) RASi reduced CRLM growth in the regenerating liver and altered immune cell composition by reducing populations of immunosuppressive MDSCs and boosting populations of PD-1+ hepatic TRMs. Thus, RASi should be explored as an adjunct therapy for patients undergoing partial hepatectomy for CRLM.