Abstract: Upon activation, mast cells rapidly release preformed inflammatory mediators from large cytoplasmic granules via regulated exocytosis. This acute degranulation is followed by a late activation phase involving synthesis and secretion of cytokines, growth factors and other inflammatory molecules via the constitutive pathway that remains ill-defined. Here the inventors describe a role for an insulin-responsive vesicle-like endosomal compartment, marked by insulin-regulated aminopeptidase (IRAP), in the secretion of TNF-? and IL-6 in mast cells and macrophages. IRAP-deficient mice are protected from TNF-dependent kidney injury and inflammatory arthritis. In the absence of IRAP, TNF fails to be efficiently exported from the Golgi. Chemical targeting of IRAP+ endosomes reduced pro-inflammatory cytokine secretion thereby highlighting this compartment as a promising target for the therapeutic control of inflammation.

Abstract: Refrigerated storage of red cell concentrates (RCC) for transfusion is associated with the accumulation of various alterations to the red blood cells (RBCs). Among these, a subpopulation of small RBCs defined as storage-induced microerythrocytes (SMEs) accumulates during storage. The SMEs subpopulation correlates with transfusion recovery. Quantification of this morphologically-altered RBC subpopulation using flow cytometry would be a valuable tool to evaluate RCC quality. In the present invention, RBC obtained at the beginning or at the end of storage from RCC stored in SAGM in blood bank conditions were treated with a carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) staining protocol and were finally analysed by flow cytometry to assess the intensity of CFSE staining. The inventors observed the accumulation of a CFDA-SEhigh subpopulation by flow cytometry that accounted for 0.8% and 36.3% at day 3 and 42 of storage, respectively.

Abstract: Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by unleashing exhausted CD8+ T-cell thereby restoring anti-tumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Here, the inventors show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T-cells, interacts and enhances PD-1 activity. In mice, CD8+ T-cell specific deletion of Nrp1 improves spontaneous and anti PD1 antibody anti-tumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T-cells QI predicts poor outcome of patients treated with anti-PD1 (e.g. pembrolizumab). Finally, the combination of anti-NRP1 and anti-PD1 antibodies is synergistic in human, specifically in CD8+ T-cells anti-tumor response. Thus the therapeutic inhibition of NRP1 alone or combined with an immune checkpoint inhibitor (e.g.

Abstract: Provided herein are methods of treating diseases associated with anemia or ineffective erythropoiesis by using the level and/or activity of a ligand of an activin receptor, in particular, Growth differentiation factor 11 (GDF11), as an indicator of responsiveness of a patient to the treatment, efficacy of the treatment, or appropriate dosage for the treatment with an activin type II receptor inhibitor.

Abstract: The present invention concerns a combination of (i) a DNA methylation inhibitor, and (ii) a Vitamin D receptor agonist, for simultaneous or sequential use in the treatment of a drug resistant cancer and/or in prevention of tumor relapse in a patient suffering from cancer. The present invention also relates to a combination of (i) a DNA methylation inhibitor, and (ii) a Vitamin D receptor agonist, for increasing, restoring or enhancing sensitivity of a patient suffering from cancer to a chemotherapeutic drug in a patient suffering from cancer.

Abstract: The present invention relates to antagonists of GDF11, for use in the treatment of malignant hematological disease, such as Acute Myeloid Leukemia (AML). The present invention also relates to a method for predicting the responsiveness of a patient affected with malignant haematological disease, such as Acute Myeloid Leukemia, to a chemotherapy treatment.

Abstract: The present invention concerns a combination of (i) a DNA methylation inhibitor, and (ii) a Vitamin D receptor agonist, for simultaneous or sequential use in the treatment of a drug resistant cancer and/or in prevention of tumor relapse in a patient suffering from cancer. The present invention also relates to a combination of (i) a DNA methylation inhibitor, and (ii) a Vitamin D receptor agonist, for increasing, restoring or enhancing sensitivity of a patient suffering from cancer to a chemotherapeutic drug in a patient suffering from cancer.

Abstract: Provided herein are methods of treating diseases associated with anemia or ineffective erythropoiesis by using the level and/or activity of a ligand of an activin receptor, in particular, Growth differentiation factor 11 (GDF11), as an indicator of responsiveness of a patient to the treatment, efficacy of the treatment, or appropriate dosage for the treatment with an activin type II receptor inhibitor.

Abstract: Provided herein are methods for the treatment of anemia, wherein the methods comprise administration of antagonists of Growth differentiation factor 11 (GDF1 1; also known as bone morphogenetic protein 11 (BMP11)) to a subject in need of the treatment.

Abstract: The present disclosure relates to antagonists of transferrin receptor and compositions and methods of use of said antagonists for treating pathological disorders such as thalassemia disorders