Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy

Abstract

The clinical responses observed following treatment with immune checkpoint inhibitors (ICIs) support immunotherapy as a potential anticancer treatment. However, a large proportion of patients cannot benefit from it due to resistance or relapse, which is most likely attributable to the multiple immunosuppressive cells in the tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSCs), a heterogeneous array of pathologically activated immature cells, are a chief component of immunosuppressive networks. These cells potently suppress T-cell activity and thus contribute to the immune escape of malignant tumors. New findings indicate that targeting MDSCs might be an alternative and promising target for immunotherapy, reshaping the immunosuppressive microenvironment and enhancing the efficacy of cancer immunotherapy. In this review, we focus primarily on the classification and inhibitory function of MDSCs and the crosstalk between MDSCs and other myeloid cells. We also briefly summarize the latest approaches to therapies targeting MDSCs.

Combination of oral STING agonist MSA-2 and anti-TGF-β/PD-L1 bispecific antibody YM101: a novel immune cocktail therapy for non-inflamed tumors

“…The non-inflamed tumor is a major challenge for cancer immunotherapy. Poor tumor immunogenicity, hampered DC maturation, suboptimal T cell priming/activation, impaired T cell infiltration, and stroma-dependent exclusion participate in immune escape and contribute to immune checkpoint resistance in non-inflamed tumors [ 46 , 47 ]. Hence, for non-inflamed tumors, a combination regimen targeting different immune escape mechanisms might be required [ 46 , 48 , 49 ].…”

The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer—Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy

“…Myeloid-derived suppressor cells (MDSCs), i.e., immature myeloid CD34 + cells, constitute an important heterogenous immunocompetent cell population of the immune suppressive intratumoral niche described in neoplastic disease, and are characterized by a strong immunosuppressive effect in both the adaptive and innate immune systems. MDSCs constitute the leading tumour promoters of carcinogenesis and are a hallmark of cancer immune evasion mechanisms [ 147 , 148 , 149 , 150 , 151 ]. Two subgroups of MDSCs have been identified based on their histological profile and cell-surface expression of specific antigens and various myeloid markers, comprising CD11b, CD33, CD14, CD15 and CD16, but lacking HLA-DR expression.…”

“…The granulocytic subset has a CD11b + LY6G + LY6C low phenotype and the monocytic subset has a CD11b + LY6G − LY6 Chi phenotype [ 148 , 152 , 153 ]. Most importantly, MDSC expansion is driven by inter alia macrophage migration inhibitory factor (MIF), cyclooxygenase 2 (COX2), prostaglandins, PGF 2 (PGLs), stem cell factor (SCF), M-CSF, IDO1, IL-6, IL-1β, IL-4, IL-13, and TNF-α, granulocyte/macrophage CSF (GM-CSF) and vascular endothelial growth factor (VEGF) [ 147 , 154 , 155 , 156 , 157 , 158 ]. These factors can activate signalling pathways in MDSCs through JAK2/STAT3 (Janus kinase protein family 2 member/signal transducer and activator of transcription 3), STAT6, nuclear factor-κB (NF-κB) and STAT1 or Notch signalling, which are key molecules involved in MDSC cell survival, proliferation, differentiation and apoptosis.…”

Evolution and Progress of mRNA Vaccines in the Treatment of Melanoma: Future Prospects

“…Immunosuppression. It has been found that cancer cells, but also myeloid-derived cells, tumor stroma cells, and CD4+ regulatory T lymphocytes, may lead to immune cell inactivation by promoting excretion of suppressive cytokines such as IL-10 (interleukin-10) and other chemical mediators such as TGF-beta (tumor growth factor-beta), which inhibit immune cell infiltration and amplification, and production of inflammatory cytokines [ 28 , 29 , 30 ].…”