Myeloid-Derived Suppressor Cells in Health and Diseases: Harnessing Their Roles in the Development of New Immunotherapy Approaches

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Background

Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell populations playing critical roles in the regulation of innate and adaptive immune responses. They represent immature myeloid precursors of monocytes, macrophages, dendritic cells and granulocytes. During emergency myelopoiesis, large numbers of MDSCs are generated from common myeloid progenitors, but their full differentiation into mature myeloid cells is halted. Moreover, in many pathological states, monocytes and immature granulocyte may also acquire MDSCs properties and functions. Thereby, these cells receive specific signals allowing them to acquire exquisite immunosuppressive functions, and to drive non-specific inflammation via the production of reactive oxygen/nitrogen species and cytokines. Up to now, MDSCs have been critically implicated in many pathological conditions, including cancer, infections, sepsis, obesity, and autoimmunity, but also in healthy conditions, such as pregnancy and aging. The roles of MDSCs in many of these conditions are still a matter of debate, illustrating the lack of strong data clarifying their specific roles.

Two major subsets of MDSC are polymorphonuclear (PMN)-MDSCs and mononuclear (M)-MDSCs. Mouse MDSCs are broadly defined as CD11b+Gr-1+ cells for PMN-MDSCs being Ly6G+Ly6Clow and M-MDSC being Ly6G-Ly6Chi. The human counterparts of MDSCs (lineage- CD11b+) are described as PMN-MDSCs CD14-CD15+/CD66b+ and M-MDSCs CD15-CD14+HLA-DR-/low, and an additional subtype termed early (e)MDSCs with CD14-CD15-phenotype, which lacks the mouse counterpart. The phenotype of MDSCs in other species has been less well defined. However, the common feature of all MDSCs is their isolation by low-density centrifugation and the suppressive properties in co-cultures with T and B cells. Although the major mechanisms of action by PMN-MDSCs and M-MDSCs have been described, the contribution of each mechanism in a particular disease is not well established. Therefore, there is a clear need for delineating specific mechanisms mediated by each MDSC subset.

Detailed investigation of MDSCs mediated mechanisms is hampered by their relatively short lifespan ex vivo. Therefore, various protocols for generating MDSCs in vitro are being investigated, which can overcome these issues. The protocols and subsequently features of these MDSC vary greatly, depending on growth factors and precursors used, and often there are no clear relations with ex vivo MDSC. Therefore, rationally designed protocols for in vitro generation of M-MDSC and PMN-MDSC are largely needed. The development of these protocols would allow the application of MDSCs as cell therapies in chronic infections, transplantation, and autoimmunity. In contrast, targeting MDSC-mediated pathological mechanisms seems a futile way of targeting cancer and sepsis. Moreover, the efficacy of many immunotherapy approaches was shown to depend on the modulation of MDSCs functions. Novel opportunities for targeting cancer were generated with the development of nanomedicine, novel natural compounds, cold atmospheric plasma (plasma medicine, an emerging field that combines plasma physics, life sciences and clinical medicine), etc. However, the role of MDSC in these therapies is still largely unknown.

In this Research Topic, we invite scientists to contribute with Reviews, Mini-Reviews and Original Research articles that will help the field to better understand the role of MDSC in health and disease, as well as to provide novel insights into potential therapeutical approaches for targeting and modulating the functions of these cells in human diseases and corresponding animal models. We welcome manuscripts focusing on, but not limited to the following topics:

• Role of MDSC in pregnancy, aging, cancer, autoimmunity, transplantation, infections, etc.

• Development of protocols for the generation of human and animal MDSC in vitro

• Mechanisms of MDSC actions in controlling the immune response

• MDSC in cell-based immunotherapy for chronic infections, autoimmunity, and transplantation

• Advanced approaches in modulating MDSC functions in pathological conditions using nanomedicines, natural components, plasma medicine, etc.

Keywords: Myeloid-Derived Suppressor Cell, MDSC, Immunological Regulation, Immunotherapy, Immunoregulation, Cancer, Autoimmunity, Pregnancy, Inflammation, Aging

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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