Targeting myeloid-derived suppressor cells for cancer therapy

Abstract

The emergence and clinical application of immunotherapy is considered a promising breakthrough in cancer treatment. According to the literature, immune checkpoint blockade (ICB) has achieved positive clinical responses in different cancer types, although its clinical efficacy remains limited in some patients. The main obstacle to inducing effective antitumor immune responses with ICB is the development of an immunosuppressive tumor microenvironment. Myeloid-derived suppressor cells (MDSCs), as major immune cells that mediate tumor immunosuppression, are intimately involved in regulating the resistance of cancer patients to ICB therapy and to clinical cancer staging and prognosis. Therefore, a combined treatment strategy using MDSC inhibitors and ICB has been proposed and continually improved. This article discusses the immunosuppressive mechanism, clinical significance, and visualization methods of MDSCs. More importantly, it describes current research progress on compounds targeting MDSCs to enhance the antitumor efficacy of ICB.

A Macrophage Differentiation-Mediated Gene: DDX20 as a Molecular Biomarker Encompassing the Tumor Microenvironment, Disease Staging, and Prognoses in Hepatocellular Carcinoma

“…As cancer progresses, the complexity of the network between tumor cells and cells of the tumor microenvironment is gradually increased [ 13 ]. Tumor biology and immunology also change over the course of the tumor transformation process and the response to immunotherapy [ 14 ].…”

“…As a major immune cell that squelches overactive antitumor immune responses in TME, myeloid-derived suppressor cell (MDSC) was closely associated with cancer patients' clinical outcomes [ 13 ]. Thus, we used TIDE arithmetic to determine the abundance of MDSC in the liver tumor at the TIMER database ( https://cistrome.shinyapps.io/timer/ ).…”

“…Cancer. As cancer progresses, the complexity of the network between tumor cells and cells of the tumor microenvironment is gradually increased [13]. Tumor biology and 8…”

Multiple Myeloma Cell-Derived Exosomes: Implications on Tumorigenesis, Diagnosis, Prognosis and Therapeutic Strategies

“…Wang et al evaluated the impact of BMSC-originated exosomes on the MM BM cells with an accent on MDSCs. MDSCs, as all immune cells that provoke immunosuppression, are closely implicated in controlling the resistance of tumor subjects to treatment and to prognosis [ 51 , 52 ].…”

The prognostic value and therapeutic targeting of myeloid-derived suppressor cells in hematological cancers

“…However, in pathological circumstances including cancer, the differentiation of precursor cells is partially blocked, leading to an accumulation of an immature myeloid cell population, defined as MDSC ( 8 , 9 ). MDSC are known to accumulate during cancer progression and promote tumor immune escape through multiple mechanisms including (i) the expression of enzymes [e.g., arginase (Arg), nitric oxide synthase (NOS), indoleamine 2,3-dioxygenase (IDO)], (ii) the release of reactive oxygen species (ROS), (iii) sequestering of cystine (↓ extracellular pool of cysteine), (iv) the interaction and stimulation of other immunosuppressive cell types (e.g., Treg) and (v) the secretion of immunosuppressive cytokines (e.g., IL-6, IL-10, TGF-β) ( 10 – 13 ).…”