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Review
. 2021 Dec 23:9:740827.
doi: 10.3389/fcell.2021.740827. eCollection 2021.

Myeloid-Derived Suppressor Cells: A Multifaceted Accomplice in Tumor Progression

Jia-Nan Cheng  1   2 , Yi-Xiao Yuan  1   2   3 , Bo Zhu  1   2 , Qingzhu Jia  1   2
Affiliations
Review

Myeloid-Derived Suppressor Cells: A Multifaceted Accomplice in Tumor Progression

Jia-Nan Cheng et al. Front Cell Dev Biol. .

Abstract

Myeloid-derived suppressor cell (MDSC) is a heterogeneous population of immature myeloid cells, has a pivotal role in negatively regulating immune response, promoting tumor progression, creating pre-metastases niche, and weakening immunotherapy efficacy. The underlying mechanisms are complex and diverse, including immunosuppressive functions (such as inhibition of cytotoxic T cells and recruitment of regulatory T cells) and non-immunological functions (mediating stemness and promoting angiogenesis). Moreover, MDSC may predict therapeutic response as a poor prognosis biomarker among multiple tumors. Accumulating evidence indicates targeting MDSC can reverse immunosuppressive tumor microenvironment, and improve therapeutic response either single or combination with immunotherapy. This review summarizes the phenotype and definite mechanisms of MDSCs in tumor progression, and provide new insights of targeting strategies regarding to their clinical applications.

Keywords: EMT; MDSC; Treg; angiogenesis; immunotherapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Development of MDSCs. MDSCs are derived from hematopoietic stem cells (HSC) in bone marrow, and differentiate into myeloid cells step by step. In the pathological conditions, a series of cytokines (GM-CSF, VEGF, IL-1β, IL-6, and IL-10) promote MDSC generation. Then suppressive MDSCs are recruited into TME by tumor-derived chemokines, such as CXCL5, CXCL8, CXCL12, CCL2, and CCL5. Further, the favorable TME accelerates the activation, survival and expansion of MDSCs. CMP, common myeloid progenitor; GMP, granulocyte and macrophage progenitor.
FIGURE 2
FIGURE 2
The roles of MDSCs in TME. MDSCs are potent suppressors of antitumor immunity. MDSCs decrease TCR expression and impair cytotoxic T cell function via producing Arg-1, NO, ROS, IL-10, and TGF-β. Moreover, MDSCs promote Tregs recruitment by secreting certain chemokines (CCL3, CCL4, and CCL5), and increase Tregs function via producing IL-10 and TGF-β. Additionally, MDSCs increase PD-L1 expression of tumor cells to mediate immune evasion. MDSCs also play non-immunological functions. MDSCs mediate EMT and stemness of tumor cells by producing VEGF, PEG2, IL-6, IL-10, and TGF-β. And MDSCs could induce angiogenesis via secreting VEGFA, FGF2, Bv8, TGF-β, IL-1β, and MMP9 to promote tumor metastasis. Strategies targeting MDSCs for cancer treatment are summarized around the main figure.
See this image and copyright information in PMC

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