Afficher la couverture 'Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. | Ghiringhelli, François' en grand format
/5

0 avis

Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors.

Archive ouverte

Ghiringhelli, François | Apetoh, Lionel | Tesniere, Antoine | Aymeric, Laetitia | Ma, Yuting | Ortiz, Carla | Vermaelen, Karim | Panaretakis, Theocharis | Mignot, Grégoire | Ullrich, Evelyn | Perfettini, Jean-Luc | Schlemmer, Frédéric | Tasdemir, Ezgi | Uhl, Martin | Génin, Pierre | Civas, Ahmet | Ryffel, Bernhard | Kanellopoulos, Jean | Tschopp, Jürg | André, Fabrice | Lidereau, Rosette | Mclaughlin, Nicole M | Haynes, Nicole M | Smyth, Mark J | Kroemer, Guido | Zitvogel, Laurence

Edité par CCSD ; Nature Publishing Group -

International audience. The therapeutic efficacy of anticancer chemotherapies may depend on dendritic cells (DCs), which present antigens from dying cancer cells to prime tumor-specific interferon-gamma (IFN-gamma)-producing T lymphocytes. Here we show that dying tumor cells release ATP, which then acts on P2X(7) purinergic receptors from DCs and triggers the NOD-like receptor family, pyrin domain containing-3 protein (NLRP3)-dependent caspase-1 activation complex ('inflammasome'), allowing for the secretion of interleukin-1beta (IL-1beta). The priming of IFN-gamma-producing CD8(+) T cells by dying tumor cells fails in the absence of a functional IL-1 receptor 1 and in Nlpr3-deficient (Nlrp3(-/-)) or caspase-1-deficient (Casp-1(-/-)) mice unless exogenous IL-1beta is provided. Accordingly, anticancer chemotherapy turned out to be inefficient against tumors established in purinergic receptor P2rx7(-/-) or Nlrp3(-/-) or Casp1(-/-) hosts. Anthracycline-treated individuals with breast cancer carrying a loss-of-function allele of P2RX7 developed metastatic disease more rapidly than individuals bearing the normal allele. These results indicate that the NLRP3 inflammasome links the innate and adaptive immune responses against dying tumor cells.

Consulter en ligne

Suggestions

Du même auteur

Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.

Archive ouverte | Apetoh, Lionel | CCSD

Conventional cancer treatments rely on radiotherapy and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. Here we show that the success of some protocols for anticancer thera...

Contribution of IL-17-producing {gamma}{delta} T cells to the efficacy of anticancer chemotherapy.

Archive ouverte | Ma, Yuting | CCSD

International audience. By triggering immunogenic cell death, some anticancer compounds, including anthracyclines and oxaliplatin, elicit tumor-specific, interferon-γ-producing CD8(+) αβ T lymphocytes (Tc1 CTLs) tha...

Calreticulin exposure dictates the immunogenicity of cancer cell death.

Archive ouverte | Obeid, Michel | CCSD

International audience. Anthracyclin-treated tumor cells are particularly effective in eliciting an anticancer immune response, whereas other DNA-damaging agents such as etoposide and mitomycin C do not induce immun...

Chargement des enrichissements...