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MDSC in Hematological Malignancies

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Myeloid-derived suppressor cells (MDSC) are a heterogeneous mixture of myeloid cells in different maturation stages that accumulate in the secondary lymphoid organs during the development of inflammatory and neoplastic diseases with the ability to suppress T-cell responses. ...

Myeloid-derived suppressor cells (MDSC) are a heterogeneous mixture of myeloid cells in different maturation stages that accumulate in the secondary lymphoid organs during the development of inflammatory and neoplastic diseases with the ability to suppress T-cell responses.
In mice, MDSCs are broadly defined as GR1+CD11b+ cells capable of suppressing antigen-specific or nonspecific T cell activation. More specifically, tumor-bearing mice can be distinguished in two main populations based on their immunophenotype and morphology: monocytic MDSCs (mo-MDSC) identified as CD11b+CD115+Ly6G-Ly6Chigh, and granulocytic MDSCs (N-MDSC) with the phenotype CD11b+CD115-Ly6G+Ly6Clow, which represent up to 75% of all MDSC.
Although the nature of N-MDSC remains largely obscure, they should be included among pathologically activated precursors of neutrophils. Indeed, N-MDSCs do not survive in culture. The presence of tumor supernatants delays their differentiation into neutrophils N-MDSC isolated from spleens of tumor-bearing mice express M-CSF and CXCR4 receptors exhibit low phagocytic activity and suppress T cell activity. In humans, MDSCs are commonly defined as Lin-CD33+HLA-DR-/low cells, or as CD14-CD11b+ cells. More recently MDSCs have also been identified within a CD15+ population in human blood.
The main mechanisms proposed to explain the MDSC- induced T-cell tolerance include the production of arginase 1 (Arg-1) and peroxyinitrites, the release of reactive oxygen species, and the induction of regulatory T cells. IL-10 production by MDSCs polarizes macrophages towards a tumor-promoting type 2 phenotype, which subsequently down-regulates naïve T cell expression of L-selectin (CD62L) and prevents naïve T cells from homing to lymph nodes where they could then be activated.
Despite deep knowledge in solid tumors, MDSC are poorly investigated in the setting of hematological malignancies, for what our Topic is addressed. We aim at creating an online dialogue on a focused research area, with manuscripts encompassing recent advancements by various groups, the latest methods, opinions and commentaries and reviews.


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