info:eu-repo/semantics/article
Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation
Fecha
2015-01-12Registro en:
Rutkowski, Melanie R.; Stephen, Tom L.; Svoronos, Nikolaos; Allegrezza, Michael J.; Tesone, Amelia J.; et al.; Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation; Cell Press; Cancer Cell; 27; 1; 12-1-2015; 27-40
1535-6108
1878-3686
CONICET Digital
CONICET
Autor
Rutkowski, Melanie R.
Stephen, Tom L.
Svoronos, Nikolaos
Allegrezza, Michael J.
Tesone, Amelia J.
Perales Puchalt, Alfredo
Brencicova, Eva
Escovar Fadul, Ximena
Nguyen, Jenny M.
Cadungog, Mark G.
Zhang, Rugang
Salatino, Mariana
Tchou, Julia
Rabinovich, Gabriel Adrián
Conejo Garcia, Jose R.
Resumen
The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism.