Analyse intégrée de la résistance dans les cancers hématologiques

The Meggetto/Pyronnet team produced an analysis of the "Omics" dataset in anaplastic large cell lymphoma. It revealed downregulation of five genes associated with crizotinib-resistance. The link between transcriptome and immunophenotype is currently under analysis. The Girard team discovered that blood vessels with similarities to high endothelial venules (HEVs) in lymph nodes, designated tumor-associated HEVs (TA-HEVs), function as major sites of lymphocyte extravasation into tumors during cancer immunity and immunotherapy with dual immune checkpoint blockade. The Sarry team METAML has shown that oxidative (OxPHOS) metabolism and mitochondrial adaptation are key mechanisms of resistance and relapse post-intensive chemotherapy (ICT) in acute myeloid leukemia (AML). The Valitutti team’s research advanced along three main lines: 1) new characterization of the lytic compartment of cytotoxic T lymphocytes; 2) new light on the molecular mechanisms by which aggressive tumors such as melanoma resist to CTL attack at the lytic synapse; 3) interdisciplinary study in which we apply computer vision to the analysis of medical and biological images. The Laurent team have recently published a new bioinformatics tool so-called ‘Single-cell spatial explorer” to measure gene set signatures. Using this tool, they have recently submitted a new study that reveals for the first time the in situ inter- and intra-MZL patient heterogeneity at both molecular and protein levels. The Martinet-Avet-Loiseau showed that NK cell with a low CD16/CD226 expression accumulate in MM patients and may be associated with MM resistance to actual treatments. A better understanding of NK and T cell landscape associated with novel MM treatment anti-CD38 monoclonal antibodies is now required and will be the focus of the next part of the project.