Myeloid-derived suppressor cells: Cancer, autoimmune diseases, and more

Abstract

Although cancer immunotherapy using immune checkpoint inhibitors (ICIs) has been recognized as one of the major treatment modalities for malignant diseases, the clinical outcome is not uniform in all cancer patients. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells that possess various strong immunosuppressive activities involving multiple immunocompetent cells that are significantly accumulated in patients who did not respond well to cancer immunotherapies. We reviewed the perspective of MDSCs with emerging evidence in this review. Many studies on MDSCs were performed in malignant diseases. Substantial studies on the participation of MDSCs on non-malignant diseases such as chronic infection and autoimmune diseases, and physiological roles in obesity, aging, pregnancy and neonates have yet to be reported. With the growing understanding of the roles of MDSCs, variable therapeutic strategies and agents targeting MDSCs are being investigated, some of which have been used in clinical trials. More studies are required in order to develop more effective strategies against MDSCs.

Keywords: MDSC; TAM; Treg; cancer; immunosuppression.

Figure 1. MDSCs generated by obesity migrate to lymphoid organ and TME.

Inflammation driven by obesity cause the differentiation of MDSC in bone marrow through proinflammatory mediators including cytokines and chemokines. MDSC migrate into tumor tissue and lymphoid organ and result in immunosuppression in TME and lymphnode. Abbreviations: FFA: free fatty acid; TNF: tumor necrosis factor; IGF: insulin-like growth factor; IL: interleukin; CCL2: CC chemokine ligand 2; GM-CSF: granulocyte-macrophage colony stimulating factor; PGE: prostaglandin E; HSC: hematopoietic stem cell; CMP: common myeloid progenitor; GMP: granulocyte-monocyte progenitor; MDSC: myeloid-derived suppressor cells; NK: natural killer; Tregs: regulatory T cells; TAM: tumor associated macrophages; TME: tumor microenvironment.

Figure 2. Potential therapeutic approaches to control myeloid-derived suppressor cells (MDSC)-driven pathological conditions of cancer, autoimmune diseases, and pregnancy.

Multiple treatment approaches have been investigated in preclinical settings and clinical trials. Suppression of MDSC activities is a goal in the field of cancer therapy. Trials using MDSCs may be effective for patients where conventional treatments with drugs were not effective. MDSCs are necessary to provide materno-fetal tolerance to pregnant women and therefore, expansion and activation of MDSCs may be effective for women with abnormal pregnancies. It was reported that estradiol and progesterone are involved in the expansion of MDSCs through STAT3. Some ideas of treatments using MDSCs for pregnancies and autoimmune diseases are still in controversial. Abbreviations: MDSC: myeloid-derived suppressor cells (monocytic, granulocytic); TME: tumor microenvironment; STAT3: signal transducer and activator of transcription 3.