Myeloid tumor necrosis factor and heme oxygenase-1 regulate the progression of colorectal liver metastases during hepatic ischemia-reperfusion.

Autor: Germanova D; Institut d'Immunologie Médicale, Université Libre de Bruxelles, Belgium.; ULB Center for Research in Immunology (U-CRI), Belgium., Keirsse J; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium., Köhler A; Institut d'Immunologie Médicale, Université Libre de Bruxelles, Belgium.; ULB Center for Research in Immunology (U-CRI), Belgium., Hastir JF; Institut d'Immunologie Médicale, Université Libre de Bruxelles, Belgium.; ULB Center for Research in Immunology (U-CRI), Belgium., Demetter P; Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium., Delbauve S; Institut d'Immunologie Médicale, Université Libre de Bruxelles, Belgium.; ULB Center for Research in Immunology (U-CRI), Belgium., Elkrim Y; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium., Verset L; Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium., Larbanoix L; Center for Microscopy and Molecular Imaging, Université de Mons, Belgium., Preyat N; Laboratory of Immunobiology, Université Libre de Bruxelles, Belgium., Laurent S; Center for Microscopy and Molecular Imaging, Université de Mons, Belgium., Nedospasov S; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences and Lomonosov Moscow State University, Moscow, Russia., Donckier V; Service de Chirurgie, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Van Ginderachter JA; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium., Flamand V; Institut d'Immunologie Médicale, Université Libre de Bruxelles, Belgium.; ULB Center for Research in Immunology (U-CRI), Belgium.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2021 Mar 01; Vol. 148 (5), pp. 1276-1288. Date of Electronic Publication: 2020 Oct 19.
DOI: 10.1002/ijc.33334
Abstrakt: The liver ischemia-reperfusion (IR) injury that occurs consequently to hepatic resection performed in patients with metastases can lead to tumor relapse for not fully understood reasons. We assessed the effects of liver IR on tumor growth and the innate immune response in a mouse model of colorectal (CR) liver metastasis. Mice subjected to liver ischemia 2 days after intrasplenic injection of CR carcinoma cells displayed a higher metastatic load in the liver, correlating with Kupffer cells (KC) death through the activation of receptor-interating protein 3 kinase (RIPK3) and caspase-1 and a recruitment of monocytes. Interestingly, the immunoregulatory mediators, tumor necrosis factor-α (TNF-α) and heme oxygenase-1 (HO-1) were strongly upregulated in recruited monocytes and were also expressed in the surviving KC following IR. Using TNF flox/flox LysM cre/wt mice, we showed that TNF deficiency in macrophages and monocytes favors tumor progression after IR. The antitumor effect of myeloid cell-derived TNF involved direct tumor cell apoptosis and a reduced expression of immunosuppressive molecules such as transforming growth factor-β, interleukin (IL)-10, inducible nitric oxyde synthase (iNOS), IL-33 and HO-1. Conversely, a monocyte/macrophage-specific deficiency in HO-1 (HO-1 flox/flox LysM cre/wt ) or the blockade of HO-1 function led to the control of tumor progression post-liver IR. Importantly, host cell RIPK3 deficiency maintains the KC number upon IR, inhibits the IR-induced innate cell recruitment, increases the TNF level, decreases the HO-1 level and suppresses the tumor outgrowth. In conclusion, tumor recurrence in host undergoing liver IR is associated with the death of antitumoral KC and the recruitment of monocytes endowed with immunosuppressive properties. In both of which HO-1 inhibition would reinforce their antitumoral activity.
(© 2020 UICC.)
Databáze: MEDLINE
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