Early T Cell Signalling Is Reversibly Altered in PD-1+ T Lymphocytes Infiltrating Human Tumors

To improve cancer immunotherapy, a better understanding of the weak efficiency of tumor-infiltrating T lymphocytes (TIL) is necessary. We have analyzed the functional state of human TIL immediately after resection of three types of tumors (NSCLC, melanoma and RCC). Several signalling pathways (calcium, phosphorylation of ERK and Akt) and cytokine secretion are affected to different extents in TIL, and show a partial spontaneous recovery within a few hours in culture. The global result is an anergy that is quite distinct from clonal anergy induced in vitro, and closer to adaptive tolerance in mice. PD-1 (programmed death -1) is systematically expressed by TIL and may contribute to their anergy by its mere expression, and not only when it interacts with its ligands PD-L1 or PD-L2, which are not expressed by every tumor. Indeed, the TCR-induced calcium and ERK responses were reduced in peripheral blood T cells transfected with PD-1. Inhibition by sodium stibogluconate of the SHP-1 and SHP-2 phosphatases that associate with several inhibitory receptors including PD-1, relieves part of the anergy apparent in TIL or in PD-1-transfected T cells. This work highlights some of the molecular modifications contributing to functional defects of human TIL

INTERET DE L'UTILISATION DU GLUCONOGLUCOHEPTONATE DE CALCIUM POUR L'EXPLORATION TOMODENSITOMETRIQUE DU GRELE ET DU COLON DANS LES MALADIES INFLAMMATOIRES DU TUBE DIGESTIF DE L'ENFANT

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Médecine générale et orthopédie dento-faciale

Certaines pathologies générales, ou agents pharmacologiques agissent sur le développement facial ou la physiologie ostéo-articulaire, modifient les paramètres du déplacement dentaire provoqué, ou peuvent augmenter le risque parodontal ou carieux. Pour le praticien en O.D.F., il est nécessaire de les identifier, car elles peuvent influencer les choix thérapeutiques, ou demander une adaptation des gestes cliniques. Cet article aborde la prise en charge de patients atteints ou présentant des antécédents de maladies fréquentes, pour qui certains actes orthodontiques sont potentiellement dangereux, ou doivent être limités