Data di Pubblicazione:
2018
Citazione:
GADD45β loss ablates innate immunosuppression in cancer / D. Verzella, J. Bennett, M. Fischietti, A.K. Thotakura, C. Recordati, F. Pasqualini, D. Capece, D. Vecchiotti, D. D'Andrea, B. Di Francesco, M.D. Maglie, F. Begalli, L. Tornatore, S. Papa, T. Lawrence, S.J. Forbes, A. Sica, E. Alesse, F. Zazzeroni, G. Franzoso. - In: CANCER RESEARCH. - ISSN 0008-5472. - 78:5(2018 Mar 01), pp. 1275-1292.
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Animals; Antigens, Differentiation; Apoptosis; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Proliferation; Female; Humans; Immune Tolerance; Liver Neoplasms; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid Cells; Neoplasms; T-Lymphocytes; Tumor Cells, Cultured; Tumor Microenvironment; Immunosuppression
Elenco autori:
D. Verzella, J. Bennett, M. Fischietti, A.K. Thotakura, C. Recordati, F. Pasqualini, D. Capece, D. Vecchiotti, D. D'Andrea, B. Di Francesco, M.D. Maglie, F. Begalli, L. Tornatore, S. Papa, T. Lawrence, S.J. Forbes, A. Sica, E. Alesse, F. Zazzeroni, G. Franzoso
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