Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy

Krishnamoorthy, Mithunah; Gerhardt, Lara; Vareki, Saman Maleki

doi:10.3390/cells10051170

Cited by 51 publications

(40 citation statements)

References 191 publications

(233 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…through the reaction of .NO and O2-inhibiting the recruitment of tumor specific T cells and leading to tumor progression [111]. Targeting of either the G-MDSC or the Mo-MDSC mechanism did not affect T cell suppression by the other pathway, suggesting that these two mechanisms acted independently to regulate T cell activity (Figure 5A, 5B).…”

Section: Role Of No In the Regulation Of Myeloid Derived Suppressor Cells (Mdscs) In The Tmementioning

confidence: 94%

“…MDSCs express high levels of indoleamine 2,3-dioxygenase 1 (IDO1) that deplete L-tryptophan and kynurenine production and lead to T cell death. MDSCs also generate nitrogen reactive species (RNS) peroxynitrite through the reaction of .NO and O2-inhibiting the recruitment of tumor specific T cells and leading to tumor progression [111]. Targeting of either the G-MDSC or the Mo-MDSC mechanism did not affect T cell suppression by the other pathway, suggesting that these two mechanisms acted independently to regulate T cell activity (Figure 5A,B).…”

Section: Role Of No In the Regulation Of Myeloid Derived Suppressor Cells (Mdscs) In The Tmementioning

confidence: 99%

See 1 more Smart Citation

Regulation of T Cells in Cancer by Nitric Oxide

Navasardyan

Bonavida

2021

Cells

View full text Add to dashboard Cite

The T cell-mediated immune response is primarily involved in the fight against infectious diseases and cancer and its underlying mechanisms are complex. The anti-tumor T cell response is regulated by various T cell subsets and other cells and tissues in the tumor microenvironment (TME). Various mechanisms are involved in the regulation of these various effector cells. One mechanism is the iNOS/.NO that has been reported to be intimately involved in the regulation and differentiation of the various cells that regulate the anti-tumor CD8 T cells. Both endogenous and exogenous .NO are implicated in this regulation. Importantly, the exposure of T cells to .NO had different effects on the immune response, depending on the .NO concentration and time of exposure. For instance, iNOS in T cells regulates activation-induced cell death and inhibits Treg induction. Effector CD8 T cells exposed to .NO result in the upregulation of death receptors and enhance their anti-tumor cytotoxic activity. .NO-Tregs suppress CD4 Th17 cells and their differentiation. Myeloid-derived suppressor cells (MDSCs) expressing iNOS inhibit T cell functions via .NO and inhibit anti-tumor CD8 T cells. Therefore, both .NO donors and .NO inhibitors are potential therapeutics tailored to specific target cells that regulate the T cell effector anti-tumor response.

show abstract

Section: Role Of No In the Regulation Of Myeloid Derived Suppressor Cells (Mdscs) In The Tmementioning

confidence: 94%

Section: Role Of No In the Regulation Of Myeloid Derived Suppressor Cells (Mdscs) In The Tmementioning

confidence: 99%

Regulation of T Cells in Cancer by Nitric Oxide

Navasardyan

Bonavida

2021

Cells

View full text Add to dashboard Cite

show abstract

“…Tumors express neoantigens that should be able to generate an immune response that recognizes and eradicates cancer cells. There are various mechanisms that suppress anti-tumor immunity [ 33 , 34 , 35 ]. Chronic inflammation is one of the key factors that cause immune suppression [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Chronic inflammation is one of the key factors that cause immune suppression [ 36 ]. One of the mechanisms through which inflammation leads to immune suppression is by recruitment of CD11b+Gr1+ myeloid derived suppressor cells (MDSC) into the tumor microenvironment [ 33 , 34 ]. CD11b+Gr1+ cells are well known to have a suppressive effect on anti-tumor immune responses [ 34 , 35 , 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor-4 Antagonist Enhances the Repair of Ultraviolet Radiation-Induced DNA Damage and Augments Anti-Tumor Immune Responses in Mice

Sherwani

Abdelgawad

Chung

et al. 2021

Cancers

View full text Add to dashboard Cite

Ultraviolet (UV) irradiation of the skin is related to the development of skin cancer. UVB also causes DNA damage in the form of cyclobutane pyrimidine dimers (CPDs), which can result in stable mutations. Toll-like receptor 4 (TLR4), a component of innate immunity, plays a key role in cancer. Previous studies from our laboratory have observed that TLR4 deficiency resulted in the repair of UVB-induced DNA damage, inhibition of UVB-induced immune suppression, and carcinogenesis. In this study, we determined the efficacy of TLR4 antagonist TAK-242 in regulation of UVB-induced DNA damage, inflammation, and tumor development. Our results indicate that TAK-242 treatment increased the expression of xeroderma pigmentosum group A (XPA) mRNA, resulting in the repair of UVB-induced CPDs in skin of SKH-1 mice. Treatment with TAK-242 also inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) in UVB-exposed skin of SKH-1 mice. Cutaneous carcinogenesis was significantly reduced in mice treated with TAK-242 in comparison to vehicle-treated mice. The proinflammatory cytokines IL-1β, IL-6, and TNF-α were also found to be significantly greater in vehicle-treated mice than TAK-242-treated mice. Finally, treatment with TAK-242 augmented anti-tumor immune responses in mice. Our data provide further evidence that activation of the TLR4 pathway promotes the development of UV-induced non-melanoma skin cancer mediated at least in part on its negative effects on DNA damage. Moreover, treatment with the TLR4 inhibitor TAK-242 may be effective for prevention of skin cancer.

show abstract

“…In most of the preclinical models discussed [119,120], it is shown that the inhibitory activity of MDSCs is specifically directed against T responses and probably NK cell responses, although it has generally not been investigated. In fact, the therapeutic effect may be thwarted in T-cell-depleted mice.…”

Section: Immunosuppressive Activity Of Mdscs On T Cell Responsesmentioning

confidence: 99%

Metabolic Rewiring in the Tumor Microenvironment to Support Immunotherapy: A Focus on Neutrophils, Polymorphonuclear Myeloid-Derived Suppressor Cells and Natural Killer Cells

et al. 2021

View full text Add to dashboard Cite

Leukocytes often undergo rapid changes in cell phenotype, for example, from a resting to an activated state, which places significant metabolic demands on the cell. These rapid changes in metabolic demand need to be tightly regulated to support immune cell effector functions during the initiation and downregulation of an immune response. Prospects for implementing cancer immunotherapy also rest on the idea of optimizing the metabolic profile of immune cell effectors. Here, we examine this issue by focusing on neutrophils and NK cells as cells of increasing interest in cancer immunology and tumor immunometabolism, because they can be targeted or, in the case of NK, used as effectors in immunotherapy. In addition, neutrophils and NK cells have been shown to functionally interact. In the case of neutrophils, we also extended our interest to polymorphonuclear MDSC (PMN-MDSCs), since the granulocytic subset of MDSCs share many phenotypes and are functionally similar to pro-tumor neutrophils. Finally, we reviewed relevant strategies to target tumor metabolism, focusing on neutrophils and NK cells.

show abstract

Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy

Cited by 51 publications

References 191 publications

Regulation of T Cells in Cancer by Nitric Oxide

Regulation of T Cells in Cancer by Nitric Oxide

Toll-Like Receptor-4 Antagonist Enhances the Repair of Ultraviolet Radiation-Induced DNA Damage and Augments Anti-Tumor Immune Responses in Mice

Metabolic Rewiring in the Tumor Microenvironment to Support Immunotherapy: A Focus on Neutrophils, Polymorphonuclear Myeloid-Derived Suppressor Cells and Natural Killer Cells

Contact Info

Product

Resources

About