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  Induction of immunosuppressive functions and NF-kappa B by FLIP in monocytes

Fiore, A., Ugel, S., De Sanctis, F., Sandri, S., Fracasso, G., Trovato, R., et al. (2018). Induction of immunosuppressive functions and NF-kappa B by FLIP in monocytes. Nature Communications, 9: 5193. doi:10.1038/s41467-018-07654-4.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-DCD4-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-DCD5-6
Genre: Journal Article

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 Creators:
Fiore, Alessandra1, Author
Ugel, Stefano1, Author
De Sanctis, Francesco1, Author
Sandri, Sara1, Author
Fracasso, Giulio1, Author
Trovato, Rosalinda1, Author
Sartoris, Silvia1, Author
Solito, Samantha1, Author
Mandruzzato, Susanna1, Author
Vascotto, Fulvia1, Author
Hippen, Keli L.1, Author
Mondanelli, Giada1, Author
Grohmann, Ursula1, Author
Piro, Geny1, Author
Carbone, Carmine1, Author
Melisi, Davide1, Author
Lawlor, Rita T.1, Author
Scarpa, Aldo1, Author
Lamolinara, Alessia1, Author
Iezzi, Manuela1, Author
Fassan, Matteo1, AuthorBicciato, Silvio1, AuthorBlazar, Bruce R.1, AuthorSahin, Ugur1, AuthorMurray, Peter J.2, Author              Bronte, Vincenzo1, Author more..
Affiliations:
1external, ou_persistent22              
2Murray, Peter / Immunoregulation, Max Planck Institute of Biochemistry, Max Planck Society, ou_2466696              

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Free keywords: MACROPHAGE DIFFERENTIATION; EXPRESSION; APOPTOSIS; CELLS; DEATH; CHEMOTHERAPY; INHIBITION; CANCER; ACTIVATION; RESISTANCEScience & Technology - Other Topics;
 Abstract: Immunosuppression is a hallmark of tumor progression, and treatments that inhibit or deplete monocytic myeloid-derived suppressive cells could promote anti-tumor immunity. c-FLIP is a central regulator of caspase-8-mediated apoptosis and necroptosis. Here we show that low-dose cytotoxic chemotherapy agents cause apoptosis linked to c-FLIP down-regulation selectively in monocytes. Enforced expression of c-FLIP or viral FLIP rescues monocytes from cytotoxicity and concurrently induces potent immunosuppressive activity, in T cell cultures and in vivo models of tumor progression and immunotherapy. FLIP-transduced human blood monocytes can suppress graft versus host disease. Neither expression of FLIP in granulocytes nor expression of other anti-apoptotic genes in monocytes conferred immunosuppression, suggesting that FLIP effects on immunosuppression are specific to monocytic lineage and distinct from death inhibition. Mechanistically, FLIP controls a broad transcriptional program, partially by NF-kappa B activation. Therefore, modulation of FLIP in monocytes offers a means to elicit or block immunosuppressive myeloid cells.

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Language(s): eng - English
 Dates: 2018
 Publication Status: Published online
 Pages: 13
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 9 Sequence Number: 5193 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723