LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells

Liang, Huaizhen; Shen, Xiaoli

doi:10.1016/j.bbrc.2020.04.137

Cited by 28 publications

(22 citation statements)

References 41 publications

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“…Liver‐X receptors (LXR) are members of the nuclear hormone receptor family that transcriptionally activate apolipoprotein E (ApoE). Treating high‐metabolic‐demand MDSCs with LXR agonists could promote apoptosis and induce dysfunction in MDSCs by potentially mediating lipoprotein metabolism 76,77 . The PMN‐MDSCs infiltrating in solid tumors show increased number of mitochondria, oxygen consumption rate and expression levels of FAO cycle enzymes such as CPT1 and 3‐hydroxyacyl‐coa dehydrogenase (HADHA) compared with the peripheral cells 73,78 .…”

Section: Lipid Metabolismmentioning

confidence: 99%

Metabolic reprogramming of myeloid-derived suppressor cells: An innovative approach confronting challenges

et al. 2021

Journal of Leukocyte Biology

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Immune cells such as T cells, macrophages, dendritic cells, and other immunoregulatory cells undergo metabolic reprogramming in cancer and inflammation-derived microenvironment to meet specific physiologic and functional demands. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are characterized by immunosuppressive activity, which plays a key role in host immune homeostasis. In this review, we have discussed the core metabolic pathways, including glycolysis, lipid and fatty acid biosynthesis, and amino acid metabolism in the MDSCs under various pathologic situations. Metabolic reprogramming is a determinant of the phenotype and functions of MDSCs, and is therefore a novel therapeutic possibility in various diseases.

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Section: Lipid Metabolismmentioning

confidence: 99%

Metabolic reprogramming of myeloid-derived suppressor cells: An innovative approach confronting challenges

et al. 2021

Journal of Leukocyte Biology

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“…More recently, in different mouse cancer models treated with specific LXRs agonists (i.e., , has been observed a slower tumor growth which correlated with a decreased expansion of myeloid derived suppressor cells (MDSCs); these data were also validated in cancer patients, in a multicentre dose escalation phase 1 trial (43). Moreover, RGX-104 also partially abrogated the immunosuppressive effects of radiotherapy in a murine model of Non-Small-Cell Lung Carcinoma (NSCLC) (104). Mechanistically, the induction of ApoE, a transcriptional target of LXR, can induce MDSC depletion by triggering the low-density lipoprotein receptorrelated 8 (LRP8) receptor on these cells, and potentiate activation of cytotoxic lymphocytes.…”

Section: Lxrs As Regulators Of Lipid Metabolism Cancer Progression mentioning

confidence: 99%

Liver X Receptors: Regulators of Cholesterol Metabolism, Inflammation, Autoimmunity, and Cancer

et al. 2020

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The interplay between cellular stress and immune response can be variable and sometimes contradictory. The mechanisms by which stress-activated pathways regulate the inflammatory response to a pathogen, in autoimmunity or during cancer progression remain unclear in many aspects, despite our recent knowledge of the signalling and transcriptional pathways involved in these diseases. In this context, over the last decade many studies demonstrated that cholesterol metabolism is an important checkpoint for immune homeostasis and cancer progression. Indeed, cholesterol is actively metabolized and can regulate, through its mobilization and/or production of active derivatives, many aspects of immunity and inflammation. Moreover, accumulation of cholesterol has been described in cancer cells, indicating metabolic addiction. The nuclear receptors liver-X-receptors (LXRs) are important regulators of intracellular cholesterol and lipids homeostasis. They have also key regulatory roles in immune response, as they can regulate inflammation, innate and adaptive immunity. Moreover, activation of LXRs has been reported to affect the proliferation and survival of different cancer cell types that show altered metabolic pathways and accumulation of cholesterol. In this minireview we will give an overview of the recent understandings about the mechanisms through which LXRs regulate inflammation, autoimmunity, and cancer, and the therapeutic potential for future treatment of these diseases through modulation of cholesterol metabolism.

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“…ApoE impedes tumor invasion and endothelial cell recruitment, but liver-X receptors (LXRs) inhibit ApoE expression. Recently, it has been reported that the LXR agonists GW3965 and RGX-104 impair MDSC survival by activating the LXR/ApoE axis and enhance the antitumor activity of CTLs [111,112]. CD33 is highly expressed on MDSCs in humans, especially M-MDSCs, but CD33 is a therapeutic target on circulating and tumor-infiltrating MDSCs across multiple cancer types [113].…”

Section: Depletion Of Mdscsmentioning

confidence: 99%

Targeting Myeloid-Derived Suppressor Cells in Cancer Immunotherapy

Wang

Jia

et al. 2020

Cancers

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Myeloid-derived suppressor cells (MDSCs), which are activated under pathological conditions, are a group of heterogeneous immature myeloid cells. MDSCs have potent capacities to support tumor growth via inhibition of the antitumoral immune response and/or the induction of immunosuppressive cells. In addition, multiple studies have demonstrated that MDSCs provide potential therapeutic targets for the elimination of immunosuppressive functions and the inhibition of tumor growth. The combination of targeting MDSCs and other therapeutic approaches has also demonstrated powerful antitumor effects. In this review, we summarize the characteristics of MDSCs in the tumor microenvironment (TME) and current strategies of cancer treatment by targeting MDSCs.

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LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells

Cited by 28 publications

References 41 publications

Metabolic reprogramming of myeloid-derived suppressor cells: An innovative approach confronting challenges

Metabolic reprogramming of myeloid-derived suppressor cells: An innovative approach confronting challenges

Liver X Receptors: Regulators of Cholesterol Metabolism, Inflammation, Autoimmunity, and Cancer

Targeting Myeloid-Derived Suppressor Cells in Cancer Immunotherapy

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