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Inflammasomes in carcinogenesis and anticancer immune responses

Abstract

In the complex interplay between malignant cells and their microenvironment, caspase-1 activation complexes (inflammasomes) have contrasting roles. Inflammasomes may operate at the cell-autonomous level to eliminate malignant precursors through programmed cell death or, conversely, may stimulate the production of trophic factors for cancer cells and their stroma. In inflammatory cells, caspase-1 activation can fuel a cycle that leads to sterile inflammation and carcinogenesis, whereas in antigen-presenting cells, inflammasomes can stimulate anticancer immune responses. The inhibition of inflammasomes or neutralization of their products, mainly interleukin 1β (IL-1β) and IL-18, has profound effects on carcinogenesis and tumor progression. Thus, inflammasomes are promising therapeutic targets in cancer-related clinical conditions. Here we discuss present and future indications for the clinical use of inflammasome inhibitors.

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Figure 1: Pyroptosis as a possible outcome of caspase-1 activation.
Figure 2: Roles of the inflammasome in carcinogenesis.
Figure 3: Implications of the inflammasome in chemotherapy-elicited anticancer immune responses.
Figure 4: Potential pharmacological targets in the inflammasome system.

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Acknowledgements

Supported by the Ligue Nationale Contre le Cancer (Equipes Labellisée; L.Z. and G.K.), Agence Nationale pour la Recherche (L.Z. and G.K.), Fondation pour la Recherche Médicale (L.Z. and G.K.), Institut National du Cancer (L.Z. and G.K.), Cancéropôle Ile-de-France (L.Z. and G.K.), the European Commission (Apo-Sys (L.Z., G.K. and L.G.), ArtForce (L.Z. and G.K.), ChemoRes (L.Z. and G.K.) and Death-Train (L.Z. and G.K.)), LabEx OncoImmunology (L.Z. and G.K.) and Institut National de la Santé et de la Recherche Médicale (O.K.).

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Correspondence to Guido Kroemer.

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Zitvogel, L., Kepp, O., Galluzzi, L. et al. Inflammasomes in carcinogenesis and anticancer immune responses. Nat Immunol 13, 343–351 (2012). https://doi.org/10.1038/ni.2224

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