Study of myeloid cells endowed with suppressive activity is an active

Study of myeloid cells endowed with suppressive activity is an active field of study which has particular importance in malignancy in view of the negative regulatory capacity of these cells to the host’s immune response. their occurrence depends on tumor-derived soluble factors which lead their development and determine their prevent of differentiation. Because of their heterogeneous composition accurate phenotyping of these cells requires a multicolor approach so that the development of all MDSC subsets can be appreciated. This review article focuses on identifying MDSCs and discusses problems associated with phenotyping circulating and tumor-associated MDSCs in humans and in mouse models. ? 2014 The Authors Cytometry Part B: Clinical Cytometry Published by Wiley Periodicals Inc. Keywords: immune suppression MDSC immunophenotyping immunology oncology Myeloid-Derived Suppressor Cells as Important Players in Regulating the Immune Response An immune response against an antigen must be properly organized to avoid an excessive response which might give rise to a harmful effect. The contraction phase of an immune response must consequently be carefully regulated and one of the mechanisms which plays a role in this phase is accomplished by myeloid-derived suppressor cells (MDSCs) a heterogeneous cell human population of myeloid cells at different phases of cell differentiation endowed with potent suppressive effects on a variety of effector cells of the immune response belonging to both innate and specific immunity. An increasing amount of evidence demonstrates the development of GDC-0980 immature myeloid cells is definitely linked to chronic and acute inflammatory processes although their recognition was originally explained in cancer. One of the hallmarks of a progressive tumor is in fact activation of irregular myelopoiesis and recruitment of immature myeloid cells (1). However it should be mentioned that MDSC development during cancer progression represents a pathological rather than a physiological event. In fact tumor cells have been demonstrated to GDC-0980 induce MDSC development by secreting tumor-derived factors (TDFs) which comprise a variety of biologically active compounds including growth CD38 factors cytokines and chemokines (2). The part of TDFs is definitely to promote not only MDSC recruitment and development but also to support myeloid cell development toward an immuno-suppressive phenotype and several lines of evidence indicate that obstructing differentiation in immature myeloid cells is one of the characteristics of this process. As discussed later in this article the differentiation step clogged in such tolerogenic cells is not clearly defined but entails cells with monocytic and granulocytic characteristics as well GDC-0980 as other immature and undifferentiated cells. In each tumor a characteristic development of one or more subsets of myeloid cells happens each of which may have various phases of differentiation but they all share a common function that is suppression of cells in the immune system. The Puzzling Query of MDSC Heterogeneity: Evidence from Mouse Studies Intensive GDC-0980 study of mouse MDSCs started in the late 1990s during experimental study on restorative anticancer vaccines. Initial observations during vaccination protocols with powerful immunogens exposed dysfunction of CD8+ cytotoxic T-lymphocytes in immuno-competent hosts (3 4 This trend was accompanied from the build up of splenic CD11b+Gr1+ cells deletion of which restored CD8+ T-cell features both in vitro and in vivo. Subsequent studies showed that these cells are endowed with great immuno-suppressive power triggered by many concurrent mechanisms (5-8). Early phenotypic characterization of murine CD11b+Gr1+ immuno-suppressive cells showed the lack of adult myeloid-associated markers and GDC-0980 morphologic observations indicated that MDSCs are a heterogeneous human population comprising monocytes polymorphonuclear cells and immature myeloid cells (9). This phenotypic and practical heterogeneity prompted experts to speculate that only a small fraction of MDSCs was endowed with immuno-suppressive activity responsible for their qualities of immune regulation (10). During the past 20 years rigorous research has led to the finding of several potential markers such as CD124 CD115 CD40 and CD80 which determine a monocytic-like portion of MDSCs accounting for most of their immune regulatory activity.