High IL-1R8 expression in breast tumors promotes tumor growth and contributes to impaired antitumor immunity.
Articolo
Data di Pubblicazione:
2017
Citazione:
High IL-1R8 expression in breast tumors promotes tumor growth and contributes to impaired antitumor immunity / L. Felipe Campesato, A.P.M. Silva, L. Cordeiro, B.R. Correa, F.C.P. Navarro, R.F. Zanin, M. Marçola, L.T. Inoue, M.L. Duarte, M. Molgora, F. Pasqualini, M. Massara, P. Galante, R. Barroso Sousa, N. Polentarutti, F. Riva, E.T. Costa, A. Mantovani, C. Garlanda, A.A. Camargo. - In: ONCOTARGET. - ISSN 1949-2553. - 30:8(2017), pp. 49470-49483. [10.18632/oncotarget.17713]
Abstract:
Tumors develop numerous strategies to fine-tune inflammation and avoid
detection and eradication by the immune system. The identification of mechanisms
leading to local immune dysregulation is critical to improve cancer therapy. We here
demonstrate that Interleukin-1 receptor 8 (IL-1R8 - previously known as SIGIRR/
TIR8), a negative regulator of Toll-Like and Interleukin-1 Receptor family signaling,
is up-regulated during breast epithelial cell transformation and in primary breast
tumors. IL-1R8 expression in transformed breast epithelial cells reduced IL-1-
dependent NF-κB activation and production of pro-inflammatory cytokines, inhibited
NK cell activation and favored M2-like macrophage polarization. In a murine breast
cancer model (MMTV-neu), IL-1R8-deficiency reduced tumor growth and metastasis
and was associated with increased mobilization and activation of immune cells, such
as NK cells and CD8+ T cells. Finally, immune-gene signature analysis in clinical
specimens revealed that high IL-1R8 expression is associated with impaired innate
immune sensing and T-cell exclusion from the tumor microenvironment. Our results
indicate that high IL-1R8 expression acts as a novel immunomodulatory mechanism
leading to dysregulated immunity with important implications for breast cancer
immunotherapy.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
L. Felipe Campesato, A.P.M. Silva, L. Cordeiro, B.R. Correa, F.C..P. Navarro, R.F. Zanin, M. Marçola, L.T. Inoue, M.L. Duarte, M. Molgora, F. Pasqualini, M. Massara, P. Galante, R. Barroso Sousa, N. Polentarutti, F. Riva, E.T. Costa, A. Mantovani, C. Garlanda, A.A. Camargo
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