Polymorphisme du systeme HLA de classe II dans la polyarthrite rhumatoiede

SIGLEINIST T 76321 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Tumor antigen-targeting monoclonal antibody-based immunotherapy: Orchestrating combined strategies for the development of long-term antitumor immunity

Tumor antigen (TA)-targeting monoclonal antibody (mAb)-based treatments are considered to be one of the most successful strategies in cancer therapy. Besides targeting TAs and inducing tumor cell death, such antibodies interact with immune cells through Fc-dependent mechanisms to induce adaptive memory immune responses. However, multiple inhibitory/immunosuppressive pathways can be induced by tumor cells to limit the establishment of an efficient antitumor response and consequently a sustained clinical response to TA-targeting mAbs. Here, we provide an overview on how TA-targeting mAbs in combination with conventional cancer therapies and/or inhibitors of key immunosuppressive pathways might represent promising approaches to achieve long-term tumor control

The emerging role of Twist proteins in hematopoietic cells and hematological malignancies

International audienceTwist1 and Twist2 (Twist1-2) are two transcription factors, members of the basic helix-loop-helix family, that have been well established as master transcriptional regulators of embryogenesis and developmental programs of mesenchymal cell lineages. Their role in oncogenesis in epithelium-derived cancer and in epithelial-to-mesenchymal transition has also been thoroughly characterized. Recently, emerging evidence also suggests a key role for Twist1-2 in the function and development of hematopoietic cells, as well as in survival and development of numerous hematological malignancies. In this review, we summarize the latest data that depict the role of Twist1-2 in monocytes, T cells and B lymphocyte activation, and in associated hematological malignancies

Polymorphism of HLA-DMA and DMB Alleles in Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organs that is characterized by the production of various antibodies against nuclear, cytoplasmic, and cell surface antigens. The expression of SLE is influenced by environmental factors and genetic predisposition 1 . Case-control studies have shown that HLA-DR2 and DR3 alleles are associated with SLE 2-5 . HLA class II regions also contain HLA-DMA and HLA-DMB genes. These 2 genes encode respectively for α and ß glycoproteins that make up the HLA-DM heterodimer involved in class II-dependent antigen presentation. To date, 4 DMAalleles and 6 DMB alleles have been described MATERIALAND METHODS Patients and controls. Seventy-three SLE patients (68 women, 5 men, median age 35 yrs, range 12-81) were examined. SLE was diagnosed by 2 rheumatologists according to the American College of Rheumatology (ACR) 1982 revised criteria 14 . All patients were of Caucasian origin. Blood was collected at the Rheumatology Department of the University Hospital of Montpellier. Two unrelated control populations were used in this study. All were healthy volunteer bone marrow donors recruited in the Montpellier area. One group consisted of 147 individuals randomly selected and typed for HLA-DR and HLA-DM genes. To determine if the association between SLE and certain HLA-DM alleles resulted from a direct influence of the DM genes or an indirect influence through linkage disequilibrium with alleles of the DRB1 locus, a second group of controls was defined. This group was composed of 86 individuals carrying DRB1*02 or DRB1*03, the SLE-associated HLA-DRB1 alleles. Methods. Genomic DNAwas extracted from peripheral blood mononuclear cells according to the classic salting-out procedure. DRB1 alleles were typed as describe

IL-21 promotes the development of a CD73-positive Vγ9Vδ2 T cell regulatory population

International audienceVγ9Vδ2 T cells contribute to the immune response against many tumor types through their direct cytotoxic activity and capacity to regulate the biological functions of other immune cells, such as dendritic cells and IFN-γ-producing CD8+ T cells. However, their presence in the tumor microenvironment has also been associated with poor prognosis in breast, colon and pancreatic cancers. Additionally, recent studies demonstrated that cytokines can confer some plasticity to Vγ9Vδ2 T cells and promote their differentiation into cells with regulatory functions. Here, we demonstrated that activation of Vγ9Vδ2 T cells isolated from healthy donors and cultured in the presence of IL-21 favors the emergence of a subpopulation of Vγ9Vδ2 T cells that express the ectonucleotidase CD73 and inhibits T cell proliferation in a CD73/adenosine-dependent manner. This subpopulation produces IL-10 and IL-8 and displays lower effector functions and cytotoxic activity than CD73-negative Vγ9Vδ2 T cells. We also showed, in a syngeneic mouse tumor model, the existence of a tumor-infiltrating γδ T cell subpopulation that produces IL-10 and strongly expresses CD73. Moreover, maturation, IL-12 production and induction of antigen-specific T cell proliferation are impaired in DC co-cultured with IL-21-amplified Vγ9Vδ2 T cells. Altogether, these data indicate that IL-21 promotes Vγ9Vδ2 T cell regulatory functions by favoring the development of an immunosuppressive CD73+ subpopulation. Thus, when present in the tumor microenvironment, IL-21 might negatively impact γδ T cell anti-tumor functions