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Captopril, a Renin-Angiotensin System Inhibitor, Attenuates Tumour Progression in the Regenerating Liver Following Partial Hepatectomy.
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.
Afiliação
  • Riddiough GE; Department of Surgery, The University of Melbourne, Austin Health, Lance Townsend Building, Level 8, 145 Studley Road, Heidelberg, VIC 3084, Australia.
  • Walsh KA; Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Fifis T; Department of Surgery, The University of Melbourne, Austin Health, Lance Townsend Building, Level 8, 145 Studley Road, Heidelberg, VIC 3084, Australia.
  • Kastrappis G; Department of Surgery, The University of Melbourne, Austin Health, Lance Townsend Building, Level 8, 145 Studley Road, Heidelberg, VIC 3084, Australia.
  • Tran BM; Department of Surgery, The University of Melbourne, Austin Health, Lance Townsend Building, Level 8, 145 Studley Road, Heidelberg, VIC 3084, Australia.
  • Vincan E; Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Muralidharan V; Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Christophi C; Victorian Infectious Disease Reference Laboratory, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Gordon CL; Curtin Medical School, Curtin University, Perth, WA 6102, Australia.
  • Perini MV; Department of Surgery, The University of Melbourne, Austin Health, Lance Townsend Building, Level 8, 145 Studley Road, Heidelberg, VIC 3084, Australia.
Int J Mol Sci ; 23(9)2022 May 09.
Article em En | MEDLINE | ID: mdl-35563674
(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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Neoplasias Hepáticas Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Neoplasias Hepáticas Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article