Captopril, a Renin-Angiotensin System Inhibitor, Attenuates Tumour Progression in the Regenerating Liver Following Partial Hepatectomy.

2022-05-09

Riddiough, Georgina E

Walsh, Katrina A

Fifis, Theodora

Kastrappis, Georgios

Tran, Bang M

Vincan, Elizabeth

Muralidharan, Vijayaragavan

Christophi, Christopher

Gordon, Claire L

Perini, Marcos V

hepatic tissue-resident memory T cells

immunology

liver neoplasms

liver regeneration

neoplasm metastasis

surgical oncology

Journal Article

0000-0003-0687-5177

0000-0002-0927-2008

0000-0002-4201-0560

0000-0002-2219-0007

0000-0002-3108-8805

0000-0002-8607-4849

0000-0002-0165-1564

0000-0001-8247-8937

0000-0002-1349-0884

#PLACEHOLDER_PARENT_METADATA_VALUE#

10.3390/ijms23095281

(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.

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International Journal of Molecular Sciences 2022; 23(9): 5281

International Journal of Molecular Sciences