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

By François Ghiringhelli, L. Apetoh, A. Tesnière, L. Aymeric, Yuting Ma, Carla Ortiz, K. Vermaelen, T. Panaretakis, G. Mignot, E. Ullrich and 16 more. Nature Medicine, 2009

1,892 citations recorded by the source corpus.

The therapeutic efficacy of anticancer chemotherapies may depend on dendritic cells (DCs), which present antigens from dying cancer cells to prime tumor-specific interferon-γ (IFN-γ)–producing T lymphocytes. Here we show that dying tumor cells release ATP, which then acts on P2X7 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-1β (IL-1β). The priming of IFN-γ–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-1β 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.

Subfields: Immunology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/f06580f6c1efe713e299b486a26a3fa1fad01f8d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Molecular Biology

In Physiology

Citations in the corpus

Cancer-related inflammation: common themes and therapeutic opportunities. (2012, result): “Associations of TLR4 and PrX7 polymorphisms with linical outcome are consistent with the relevance of these pathays [85].”
Inflammation and Cancer: Triggers, Mechanisms and Consequences (2019, background): “This along with increased release of tumor neo-antigens this may induce and sustain de novo anti-tumor T cell responses (Ghiringhelli et al., 2009) or may lead to immunosuppression (Hou et al., 2017).”
Drug resistance and combating drug resistance in cancer (2019, background): “It is also conceivable that alteration of extracellular ATP levels may further enhance cancer immunotherapy, as immune cells in tumors are sensitive to ATP levels([188-193]).”