GADD45β loss ablates innate immunosuppression in cancer

Daniela Verzella, Jason Bennett, Mariafausta Fischietti, Anil K. Thotakura, Camilla Recordati, Fabio Pasqualini, Daria Capece, Davide Vecchiotti, Daniel D'Andrea, Barbara Di Francesco, Marcella De Maglie, Federica Begalli, Laura Tornatore, Salvatore Papa, Toby Lawrence, Stuart J. Forbes, Antonio Sica, Edoardo Alesse, Francesca Zazzeroni, Guido Franzoso

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

T-cell exclusion from the tumor microenvironment (TME) is a major barrier to overcoming immune escape. Here, we identify a myeloid-intrinsic mechanism governed by the NF-κB effector molecule GADD45b that restricts tumor-associated inflammation and T-cell trafficking into tumors. In various models of solid cancers refractory to immunotherapies, including hepatocellular carcinoma and ovarian adenocarcinoma, Gadd45b inhibition in myeloid cells restored activation of proinflammatory tumor-associated macrophages (TAM) and intratumoral immune infiltration, thereby diminishing oncogenesis. Our results provide a basis to interpret clinical evidence that elevated expression of GADD45B confers poorclinical outcomes in most human cancers. Furthermore, they suggest a therapeutic target in GADD45β for reprogramming TAM to overcome immunosuppression and T-cell exclusion from the TME.

Lingua originaleInglese
pagine (da-a)1275-1292
Numero di pagine18
RivistaCancer Research
Volume78
Numero di pubblicazione5
DOI
Stato di pubblicazionePubblicato - 1 mar 2018

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