Artículo
Targeting TMEM176B enhances antitumor immunity and augments the efficacy of immune checkpoint blockers by unleashing inflammasome activation
Segovia, Mercedes; Russo, Sofia; Jeldres, Mathias; Mahmoud, Yamil Damián
; Perez, Valentina; Duhalde, Maite; Charnet, Pierre; Rousset, Matthieu; Victoria, Sabina; Veigas, Florenci; Louvet, Cédric; Vanhove, Bernard; Floto, R. Andrés; Anegon, Ignacio; Cuturi, Maria Cristina; Girotti, Maria Romina
; Rabinovich, Gabriel Adrián
; Hill, Marcelo
Fecha de publicación:
05/2019
Editorial:
Cell Press
Revista:
Cancer Cell
ISSN:
1535-6108
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Although immune checkpoint blockers have yielded significant clinical benefits in patients with different malignancies, the efficacy of these therapies is still limited. Here, we show that disruption of transmembrane protein 176B (TMEM176B)contributes to CD8 + T cell-mediated tumor growth inhibition by unleashing inflammasome activation. Lack of Tmem176b enhances the antitumor activity of anti-CTLA-4 antibodies through mechanisms involving caspase-1/IL-1β activation. Accordingly, patients responding to checkpoint blockade therapies display an activated inflammasome signature. Finally, we identify BayK8644 as a potent TMEM176B inhibitor that promotes CD8 + T cell-mediated tumor control and reinforces the antitumor activity of both anti-CTLA-4 and anti-PD-1 antibodies. Thus, pharmacologic de-repression of the inflammasome by targeting TMEM176B may enhance the therapeutic efficacy of immune checkpoint blockers.
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Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
Segovia, Mercedes; Russo, Sofia; Jeldres, Mathias; Mahmoud, Yamil Damián; Perez, Valentina; et al.; Targeting TMEM176B enhances antitumor immunity and augments the efficacy of immune checkpoint blockers by unleashing inflammasome activation; Cell Press; Cancer Cell; 35; 5; 5-2019; 767-781
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