Abstract
Immature myeloid cells at varied stages of differentiation, known as myeloid-derived suppressor cells (MDSC), are present in virtually all cancer patients. MDSC are profoundly immune-suppressive cells that impair adaptive and innate antitumor immunity and promote tumor progression through nonimmune mechanisms. Their widespread presence combined with their multitude of protumor activities makes MDSC a major obstacle to cancer immunotherapies. MDSC are derived from progenitor cells in the bone marrow and traffic through the blood to infiltrate solid tumors. Their accumulation and suppressive potency are driven by multiple tumor- and host-secreted proinflammatory factors and adrenergic signals that act via diverse but sometimes overlapping transcriptional pathways. MDSC also accumulate in response to the chronic inflammation and lipid deposition characteristic of obesity and contribute to the more rapid progression of cancers in obese individuals. This article summarizes the key aspects of tumor-induced MDSC with a focus on recent progress in the MDSC field.
Highlights
Checkpoint blockade immunotherapy (CBI) has revolutionized cancer therapy and has demonstrated that a patient’s adaptive immune system can eradicate malignant cells provided immunesuppressive mechanisms are neutralized (Park & Youn 2019, Tavazoie et al 2018)
Studies in triple-negative breast cancer revealed that the tumor microenvironment (TME) drives aerobic glycolysis in tumor cells, upregulating AMPK and activating the liver-enriched activator protein (LAP) isoform of C/EBPβ, resulting in production of Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (Li et al 2018)
myeloid-derived suppressor cells (MDSC) are a profoundly immune-suppressive population of myeloid cells that are present in most cancer patients
Summary
Checkpoint blockade immunotherapy (CBI) has revolutionized cancer therapy and has demonstrated that a patient’s adaptive immune system can eradicate malignant cells provided immunesuppressive mechanisms are neutralized (Park & Youn 2019, Tavazoie et al 2018). The low-grade inflammation associated with ageing is accompanied by induction of MDSC in mice and probably in humans (Flores et al 2017, Pawelec et al 2019, Verschoor et al 2013). Given their potent immunesuppressive activity, MDSC are being exploited to retain allogeneic grafts (Nakamura & Ushigome 2018). The term “MDSC” was originally ascribed to human and mouse immature cells of myeloid lineage that have immune-suppressive activity and are elevated in experimental animals and patients with cancer (Gabrilovich et al 2007).
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