Advanced search
1 file | 2.97 MB Add to list

Hepatocarcinoma induces a tumor necrosis factor-dependent Kupffer cell death pathway that favors its proliferation upon partial hepatectomy

Author
Organization
Abstract
Partial hepatectomy (PH) is the main treatment for early-stage hepatocellular carcinoma (HCC). Yet, a significant number of patients undergo recursion of the disease that could be linked to the fate of innate immune cells during the liver regeneration process. In this study, using a murine model, we investigated the impact of PH on HCC development by bioluminescence imaging and flow cytometry. While non-resected mice were able to control and reject orthotopic implanted Hepa1-6 hepatocarcinoma cells, resected liver underwent an increased tumoral proliferation. This phenomenon was associated with a PH-induced reduction in the number of liver-resident macrophages, i.e., Kupffer cells (KC). Using a conditional ablation model, KC were proved to participate in Hepa1-6 rejection. We demonstrated that in the absence of Hepa1-6, PH-induced KC number reduction was dependent on tumor necrosis factor-alpha (TNF-alpha), receptor-interacting protein kinase (RIPK) 3, and caspase-8 activation, whereas interleukin (IL)-6 acted as a KC pro-survival signal. In mice with previous Hepa1-6 encounter, the KC reduction switched toward a TNF-alpha-RIPK3-caspase-1 activation. Moreover, KC disappearance associated with caspase-1 activity induced the recruitment of monocyte-derived cells that are beneficial for tumor growth, while caspase-8-dependent reduction did not. In conclusion, our study highlights the importance of the TNF-alpha-dependent death pathway induced in liver macrophages following partial hepatectomy in regulating the antitumoral immune responses.
Keywords
CHEMOKINE LIGAND 2, ANTI-TNF THERAPY, NF-KAPPA-B, HEPATOCELLULAR-CARCINOMA, LIVER-REGENERATION, MONOCLONAL-ANTIBODY, HEART-FAILURE, RISK-FACTORS, FACTOR-ALPHA, MACROPHAGES, Kupffer cells, hepatocellular carcinoma, liver regeneration, partial, hepatectomy, cell death, inflammation, tumor necrosis factor-alpha

Downloads

  • 4441 20Hastir.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 2.97 MB

Citation

Please use this url to cite or link to this publication:

MLA
Hastir, Jean-Francois, et al. “Hepatocarcinoma Induces a Tumor Necrosis Factor-Dependent Kupffer Cell Death Pathway That Favors Its Proliferation upon Partial Hepatectomy.” FRONTIERS IN ONCOLOGY, vol. 10, 2020, doi:10.3389/fonc.2020.547013.
APA
Hastir, J.-F., Delbauve, S., Larbanoix, L., Germanova, D., Goyvaerts, C., Allard, J., … Flamand, V. (2020). Hepatocarcinoma induces a tumor necrosis factor-dependent Kupffer cell death pathway that favors its proliferation upon partial hepatectomy. FRONTIERS IN ONCOLOGY, 10. https://doi.org/10.3389/fonc.2020.547013
Chicago author-date
Hastir, Jean-Francois, Sandrine Delbauve, Lionel Larbanoix, Desislava Germanova, Cleo Goyvaerts, Justine Allard, Sophie Laurent, et al. 2020. “Hepatocarcinoma Induces a Tumor Necrosis Factor-Dependent Kupffer Cell Death Pathway That Favors Its Proliferation upon Partial Hepatectomy.” FRONTIERS IN ONCOLOGY 10. https://doi.org/10.3389/fonc.2020.547013.
Chicago author-date (all authors)
Hastir, Jean-Francois, Sandrine Delbauve, Lionel Larbanoix, Desislava Germanova, Cleo Goyvaerts, Justine Allard, Sophie Laurent, Karine Breckpot, Alain Beschin, Martin Guilliams, and Veronique Flamand. 2020. “Hepatocarcinoma Induces a Tumor Necrosis Factor-Dependent Kupffer Cell Death Pathway That Favors Its Proliferation upon Partial Hepatectomy.” FRONTIERS IN ONCOLOGY 10. doi:10.3389/fonc.2020.547013.
Vancouver
1.
Hastir J-F, Delbauve S, Larbanoix L, Germanova D, Goyvaerts C, Allard J, et al. Hepatocarcinoma induces a tumor necrosis factor-dependent Kupffer cell death pathway that favors its proliferation upon partial hepatectomy. FRONTIERS IN ONCOLOGY. 2020;10.
IEEE
[1]
J.-F. Hastir et al., “Hepatocarcinoma induces a tumor necrosis factor-dependent Kupffer cell death pathway that favors its proliferation upon partial hepatectomy,” FRONTIERS IN ONCOLOGY, vol. 10, 2020.
@article{8683294,
  abstract     = {Partial hepatectomy (PH) is the main treatment for early-stage hepatocellular carcinoma (HCC). Yet, a significant number of patients undergo recursion of the disease that could be linked to the fate of innate immune cells during the liver regeneration process. In this study, using a murine model, we investigated the impact of PH on HCC development by bioluminescence imaging and flow cytometry. While non-resected mice were able to control and reject orthotopic implanted Hepa1-6 hepatocarcinoma cells, resected liver underwent an increased tumoral proliferation. This phenomenon was associated with a PH-induced reduction in the number of liver-resident macrophages, i.e., Kupffer cells (KC). Using a conditional ablation model, KC were proved to participate in Hepa1-6 rejection. We demonstrated that in the absence of Hepa1-6, PH-induced KC number reduction was dependent on tumor necrosis factor-alpha (TNF-alpha), receptor-interacting protein kinase (RIPK) 3, and caspase-8 activation, whereas interleukin (IL)-6 acted as a KC pro-survival signal. In mice with previous Hepa1-6 encounter, the KC reduction switched toward a TNF-alpha-RIPK3-caspase-1 activation. Moreover, KC disappearance associated with caspase-1 activity induced the recruitment of monocyte-derived cells that are beneficial for tumor growth, while caspase-8-dependent reduction did not. In conclusion, our study highlights the importance of the TNF-alpha-dependent death pathway induced in liver macrophages following partial hepatectomy in regulating the antitumoral immune responses.},
  articleno    = {547013},
  author       = {Hastir, Jean-Francois and Delbauve, Sandrine and Larbanoix, Lionel and Germanova, Desislava and Goyvaerts, Cleo and Allard, Justine and Laurent, Sophie and Breckpot, Karine and Beschin, Alain and Guilliams, Martin and Flamand, Veronique},
  issn         = {2234-943X},
  journal      = {FRONTIERS IN ONCOLOGY},
  keywords     = {CHEMOKINE LIGAND 2,ANTI-TNF THERAPY,NF-KAPPA-B,HEPATOCELLULAR-CARCINOMA,LIVER-REGENERATION,MONOCLONAL-ANTIBODY,HEART-FAILURE,RISK-FACTORS,FACTOR-ALPHA,MACROPHAGES,Kupffer cells,hepatocellular carcinoma,liver regeneration,partial,hepatectomy,cell death,inflammation,tumor necrosis factor-alpha},
  language     = {eng},
  pages        = {13},
  title        = {Hepatocarcinoma induces a tumor necrosis factor-dependent Kupffer cell death pathway that favors its proliferation upon partial hepatectomy},
  url          = {http://dx.doi.org/10.3389/fonc.2020.547013},
  volume       = {10},
  year         = {2020},
}

Altmetric
View in Altmetric
Web of Science
Times cited: