Objectif There is increasing evidence that the body s ability to mount an immune response to cancer cells may dictate which patients are cured of cancer by conventional therapy. Macrophages have a central role in both innate and adaptive immunity; both human and experimental cancers become infiltrated by macrophages, however tumour-associated macrophages (TAM) are corrupted by the tumour microenvironment to promote survival, invasion and metastasis of cancer cells. TAM also contribute to immune-suppression in cancer and evasion of anti-tumour immunity. It is not clear what factors promote the pro-tumour TAM phenotype or the signalling pathways involved. The intrinsic anti-tumour potential of macrophages as innate immune cells and their abundance in solid tumours makes them an attractive therapeutic target. The challenge is to block the cancer-promoting function of these cells and restore their anti-tumour effects. We have previously shown that NF-ºB inhibits the classical activation of macrophages in the context of inflammation and cancer and our preliminary data show that NF-ºB activation in TAM inhibits anti-tumour immunity in transplantable models of cancer. Further studies have shown a subset of IKK²-regulated genes in macrophages are dependent on p38 MAP Kinase (MAPK14) and targeting p38 activity in macrophages also blocks the TAM phenotype. These data suggest IKK²-p38 signalling maintains the pro-tumour phenotype of TAM and inhibits anti-tumour immunity.In this project we will extend our preliminary observations in transplantable tumour models to clinically relevant genetic models of spontaneous cancer in mice. We will also map IKK² and p38 target genes in TAM and investigate IKK²/p38 dependent mechanisms of gene regulation. Champ scientifique medical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicineoncology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2010-StG_20091118 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Contribution de l’UE € 1 499 222,00 Adresse RUE DE TOLBIAC 101 75654 Paris France Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Contact administratif Veronique Legros (Ms.) Chercheur principal Toby Lawrence (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France Contribution de l’UE € 1 499 222,00 Adresse RUE DE TOLBIAC 101 75654 Paris Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Contact administratif Veronique Legros (Ms.) Chercheur principal Toby Lawrence (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
