High-mobility group box protein 1 promotes the survival of myeloid-derived suppressor cells by inducing autophagy

Parker, Katherine H.; Horn, Lucas A.; Ostrand‐Rosenberg, Suzanne

doi:10.1189/jlb.3hi0715-305r

Cited by 61 publications

(58 citation statements)

References 44 publications

(53 reference statements)

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“…Several mechanisms have been identified that regulate MDSC survival. Inflammation, and particularly IL-1β [81, 82] and HMGB1 [95] not only drives MDSC accumulation but also extends their half-life. Mechanistically, increased survival has been attributed to miRNA-494 through its ability to activate the AKT pathway [96], and to activation of the transcription factor Nrf2, which up-regulates anti-oxidant genes and protects MDSC from ROS [97].…”

Section: Therapies That Universally Neutralize Mdsc Are Neededmentioning

confidence: 99%

Tolerance and immune suppression in the tumor microenvironment

Ostrand‐Rosenberg

2016

Cellular Immunology

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The concept of immunological tolerance has guided and permeated much of modern immunology. Ray Owen’s ground-breaking observations in twin cattle provided the first mechanistic explanation for tolerance to self-molecules and established tolerance as a beneficial process that protects the host against autoreactivity. However, his studies also opened the door to understanding that tolerance may be detrimental, such as occurs when cancer cells induce tolerance/immune suppression resulting in inhibition of anti-tumor immunity. This article briefly traces the early history of the field of tumor immunology with respect to tolerance, and then focuses on a relatively recently identified population of cells called myeloid-derived suppressor cells (MDSC). MDSC are instrumental in causing tolerance/immune suppression in individuals with cancer. They are present in most individuals with cancer and because of their potent immune suppressive activity are a major deterrent to natural anti-tumor immunity and a significant obstacle to immunotherapy.

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Section: Therapies That Universally Neutralize Mdsc Are Neededmentioning

confidence: 99%

Tolerance and immune suppression in the tumor microenvironment

Ostrand‐Rosenberg

2016

Cellular Immunology

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“…Although G‐MDSC and M‐MDSC could both impede T cell responses, the latter was more suppressive . Except for immunosuppressive effects on cancer development, more evidence showed that MDSC could accelerate the development of cancers by inducing autophagy, reprogramming metabolic status and supporting cancer cell stemness . It remains unclear whether RSV also modulated M‐MDSC in other cancer‐bearing mice models.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol ameliorates Lewis lung carcinoma‐bearing mice development, decreases granulocytic myeloid‐derived suppressor cell accumulation and impairs its suppressive ability

et al. 2018

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Myeloid‐derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells which consist of 2 subsets: granulocytic MDSC (G‐MDSC) and monocytic MDSC (M‐MDSC). MDSC expand in tumor‐bearing hosts and contribute to immunotherapeutic resistance by remarkably blocking effector T‐cell activation via different mechanisms. Resveratrol (RSV) is a polyphenol and it has been widely used for its various health benefits. However, the underlying mechanism of its anti‐tumor properties remains unclear. In this study, a transplantable mouse model was used to investigate the effects of RSV on MDSC. The results showed that RSV ameliorated tumor development by decreasing G‐MDSC accumulation, impairing its suppressive ability on CD8+T cells and promoting M‐MDSC differentiation into CD11c+ and F4/80+ cells. Our results indicated that RSV should be considered as a modular of MDSC suppressive function and that RSV is a novel booster for tumor immunotherapy.

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“…Nevertheless, these in vitro data just give hints that an immune stimulatory microenvironment is created when combining RT with a further stressor such as heat. HMGB1 for example also regulates myeloid‐derived suppressor cell (MDSC) survival through induction of autophagy . In the next step, we therefore set up local irradiation and heating procedures of B16‐F10 tumor‐bearing C57/BL6 mice that closely resemble the clinical situation.…”

Section: Impact Of Radiation and Additional Immune Modulators On The mentioning

confidence: 99%

“…HMGB1 for example also regulates myeloid-derived suppressor cell (MDSC) survival through induction of autophagy. 57 In the next step, we therefore set up local irradiation and heating procedures of B16-F10 tumor-bearing C57/BL6 mice that closely resemble the clinical situation. Combined treatment of the ectopic tumors with RT and HT enhanced the infiltration of DCs,…”

Section: Hyperthermia As Second Stimulus For Rt To Create An Immunementioning

confidence: 99%

Immunomodulation by ionizing radiation—impact for design of radio‐immunotherapies and for treatment of inflammatory diseases

Frey

Rückert

Deloch

et al. 2017

Immunological Reviews

152

127

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Ionizing radiation is often regarded as an element of danger. But, danger responses on the cellular and molecular level are often beneficial with regard to the induction of anti-tumor immunity and for amelioration of inflammation. We outline how in dependence of radiation dose and fraction, radiation itself-and especially in combination with immune modulators-impacts on the innate and adaptive immune system. Focus is set on radiation-induced changes of the tumor cell phenotype and the cellular microenvironment including immunogenic cancer cell death. Mechanisms how anti-tumor immune responses are triggered by radiotherapy in combination with hyperthermia, inhibition of apoptosis, the adjuvant AnnexinA5, or vaccination with high hydrostatic pressure-killed autologous tumor cells are discussed. Building on this, feasible multimodal radio-immunotherapy concepts are reviewed including overcoming immune suppression by immune checkpoint inhibitors and by targeting TGF-β. Since radiation-induced tissue damage, inflammation, and anti-tumor immune responses are interconnected, the impact of lower doses of radiation on amelioration of inflammation is outlined. Closely meshed immune monitoring concepts based on the liquid biopsy blood are suggested for prognosis and prediction of cancer and non-cancer inflammatory diseases. Finally, challenges and visions for the design of cancer radio-immunotherapies and for treatment of benign inflammatory diseases are given.

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High-mobility group box protein 1 promotes the survival of myeloid-derived suppressor cells by inducing autophagy

Cited by 61 publications

References 44 publications

Tolerance and immune suppression in the tumor microenvironment

Tolerance and immune suppression in the tumor microenvironment

Resveratrol ameliorates Lewis lung carcinoma‐bearing mice development, decreases granulocytic myeloid‐derived suppressor cell accumulation and impairs its suppressive ability

Immunomodulation by ionizing radiation—impact for design of radio‐immunotherapies and for treatment of inflammatory diseases

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