Myeloid‐Derived Suppressor Cells and Therapeutic Strategies in Cancer

Abstract

Development of solid cancer depends on escape from host immunosurveillance. Various types of immune cells contribute to tumor-induced immune suppression, including tumor associated macrophages, regulatory T cells, type 2 NKT cells, and myeloid-derived suppressor cells (MDSCs). Growing body of evidences shows that MDSCs play pivotal roles among these immunosuppressive cells in multiple steps of cancer progression. MDSCs are immature myeloid cells that arise from myeloid progenitor cells and comprise a heterogeneous immune cell population. MDSCs are characterized by the ability to suppress both adaptive and innate immunities mainly through direct inhibition of the cytotoxic functions of T cells and NK cells. In clinical settings, the number of circulating MDSCs is associated with clinical stages and response to treatment in several cancers. Moreover, MDSCs are reported to contribute to chemoresistant phenotype. Collectively, targeting MDSCs could potentially provide a rationale for novel treatment strategies in cancer. This review summarizes recent understandings of MDSCs in cancer and discusses promissing clinical approaches in cancer patients.

mRNA-based dendritic cell immunization improves survival inrettransgenic mouse melanoma model

“…20 Another crucial immunosuppressive cell population is represented by MDSCs that inhibit antitumor T-cell responses by multiple mechanisms and can be considered as one of the most important components of tumor-induced immunosuppression in melanoma. 14,15,32,33 It has been previously described that MDSCs accumulate in peripheral lymphoid organs and migrate to tumor sites, where they contribute to immunosuppression. 15,16,33,34 Furthermore, some evidence suggests that MDSCs can induce an expansion of Tregs.…”

Potential Anticancer Drugs Targeting Immune Pathways

“…Treatment in patients with head and neck squamous cell carcinoma resulted in reduction of the circulating CD34 + MDSCs with increased levels of plasma IL-12 and IFN-γ and T-cell proliferation. However, in another study, 25-hydroxyvitamin D 3 alone has failed to improve the clinical outcome [52,53].…”

“…Treatment of ATRA on mouse or human MDSCs results in the induction of myeloid cell differentiation both in vitro and in vivo and thereby improves antitumor immune responses [51]. However, ATRA was also shown to induce the development of CD4 + regulatory T cells (Tregs), by upregulating expression of the T cell cell-fate regulatory transcription factor FoxP3 [52]. Thus, ATRA is not an ideal candidate for MDSC depletion, as simultaneous Treg induction induced by ATRA treatment could further contribute to tumor development.…”

“…Thus, ATRA is not an ideal candidate for MDSC depletion, as simultaneous Treg induction induced by ATRA treatment could further contribute to tumor development. Another promoter of MDSCs differentiation is 25-dihydroxyvitamin D3, which has been reported to drive myeloid progenitor cell differentiation both in vitro and in vivo [52,53]. Treatment in patients with head and neck squamous cell carcinoma resulted in reduction of the circulating CD34 + MDSCs with increased levels of plasma IL-12 and IFN-γ and T-cell proliferation.…”

Towards tumor immunodiagnostics

“…Human MDSCs express the myeloid markers CD33 and CD11b, are HLA-DR negative, with the myeloid and the monocytic precursors also expressing CD15 and CD14, respectively (68,69).…”