Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are activated under pathological conditions, such as cancer, or mature myeloid cells that are converted immune-suppressive cells via tumor-derived exosomes, and potently support the tumor processes at different levels. Currently, multiple studies have demonstrated that MDSCs induce immune checkpoint blockade (ICB) therapy resistance through their contribution to the immunosuppressive network in the tumor microenvironment. In addition, non-immunosuppressive mechanisms of MDSCs such as promotion of angiogenesis and induction of cancer stem cells also exert a powerful role in tumor progression. Thus, MDSCs are potential therapeutic targets to enhance the antitumor efficacy of ICB therapy in cases of multiple cancers. This review focuses on the tumor-promoting mechanism of MDSCs and provides an overview of current strategies that target MDSCs with the objective of enhancing the antitumor efficacy of ICB therapy.
Highlights
Myeloid-derived suppressor cells (MDSCs) are broadly defined as a heterogeneous population of immature myeloid cells sharing many phenotypic markers with monocytes, macrophages, and dendritic cells (DCs), leading a powerful immunosuppressive role in the tumor microenvironment (TME)
Because MDSCs expansion is known to be regulated by tumorderived factors, several studies have focused on neutralizing the effects of these factors to improve the efficiency of immune checkpoint blockade (ICB)
Small extracellular vesicles derived from the hypoxic tumor microenvironment of head and neck squamous cell carcinoma (HNSCC) recruited MDSCs to form a premetastatic niche by delivering lysyl oxidase like 2 (LOXL2) to fibroblasts to induce fibronectin production [134]
Summary
Myeloid-derived suppressor cells (MDSCs) are broadly defined as a heterogeneous population of immature myeloid cells sharing many phenotypic markers with monocytes, macrophages, and dendritic cells (DCs), leading a powerful immunosuppressive role in the tumor microenvironment (TME). Some studies have reported that normal monocytes could be converted to MDSC via tumor-derived exosomes [1]; MDSCs represent immature and mature myeloid cells. ICB employs antibody-based therapies targeting these checkpoints in an effort to unleash preexisting adaptive immunity [5]. It is clear from large clinical trials that therapeutic resistance occurs in numbers of patients leading to progression [6,7,8]. We summarize therapeutic strategies targeting them to enhance the antitumor activity of ICB therapy
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