Poster No. 101 Drastic Decreased Expression of Activating Receptors on NK Cells in Human Lung Tumor Microenvironment Impairs their Cytotoxic Functions Sophia Platonova 1 , Julien Cherfils-Vicini1, Liana Ghazarian1, Pierre Validire1,2, Vincent Vieillard4, Wolf Herman Fridman1, Catherine Sautès-Fridman1, Diane Damotte 1,3, Isabelle Cremer1 1 INSERM U872 Team 13, Centre de Recherche des Cordeliers, Paris, France, 2 Pathological Anatomy Service, Intitut Mutualiste Montsouris, Bcl-2 inhibitor Paris, France, 3 Pathological Anatomy Service, Hôpital Hôtel Dieu, Paris, France, 4 INSERM U543, Paris, France While
NK cells were originally identified by their ability to kill tumor cells in vitro, only limited information is available on NK cells present in tumor microenvironment. Our objectives were to characterize 4EGI-1 order the phenotype and function of NK cells in human Non Small Cell Lung Cancers (NSCLC) patients, in tumor microenvironment, in non tumoral lung tissue, and in the blood, and to investigate the expression
of NK cell receptor ligands on tumor cells. NK cells are present both in tumoral and non tumoral lung tissues of NSCLC patients. In the tumor, they are mainly localised in the invasive margin, but outside tertiary lymphoid structures (Ti-BALT – “Tumor-induced Bronchus Associated Glycogen branching enzyme Lymphoid Tissues”) that are induced in the tumoral area. Intratumoral NK cells are not cytotoxic even after activation with IL-2,
on the contrary to NK cells from blood of the same patient, despite an activated phenotype defined by NKp44 and CD69 expression. Consistent with this observation, intratumoral NK cells display a highly significant decreased expression of activating receptors such as NKG2D, NKp30, NKp80, DNAM-1 and CD16. On the contrary, NK cells from non tumoral lung tissue or blood of NSCLC patients have the same phenotype than healthy Daporinad nmr donors. Analysis of NK cell receptor ligand expression revealed that inhibitory receptors ligands such as HLA-G and HLA-E are strongly expressed by tumor cells, but not by normal tissue, whereas activating receptors ligands such as MICA/B and ULBP1, 2, 3 are rarely expressed by tumor cells. Altogether these results demonstrate for the first time that the NK cells display an altered phenotype and function specifically in the tumor microenvironment and that tumor cells express high levels of inhibitory receptors ligands. This suggests a local induction of escape mechanisms established by tumor cells and directed towards NK cells. Poster No.