Journal article

TNF Receptor-2 Facilitates an Immunosuppressive Microenvironment in the Liver to Promote the Colonization and Growth of Hepatic Metastases

Boram Ham, Ni Wang, Zarina D'Costa, Maria Celia Fernandez, France Bourdeau, Patrick Auguste, Martin Illemann, Rikke Loevendahl Eefsen, Gunilla Hoyer-Hansen, Ben Vainer, Maximilien Evrard, Zu-Hua Gao, Pnina Brodt



Successful colonization by a cancer cell of a distant metastatic site requires immune escape in the new microenvironment. TNF signaling has been implicated broadly in the suppression of immune surveillance that prevents colonization at the metastatic site and therefore must be blocked. In this study, we explored how TNF signaling influences the efficiency of liver metastasis by colon and lung carcinoma in mice that are genetically deficient for the TNF receptor TNFR2. We found a marked reduction in liver metastases that correlated with a greatly reduced accumulation at metastatic sites of CD11b(+)GR-1(+) myeloid cells with enhanced arginase activity, identified as myeloid-derived suppressor ..

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Awarded by Canadian Institute for Health Research

Awarded by Quebec Ministere de l'Economie, de l'Innovation et des Exportations

Funding Acknowledgements

This study was supported by grants MOP-80201 from the Canadian Institute for Health Research and a PSR-SIIRI-843 grant from the Quebec Ministere de l'Economie, de l'Innovation et des Exportations (P. Brodt), by McGill Integrated Cancer Research Training Program fellowships (B. Ham and M.C. Fernandez) and by Faculty of Internal Medicine-Peter Quinlan Fellowship in Oncology (Z. D'Costa).