Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1

Roux, Cecilia; Jafari, Soode Moghadas; Shinde, Rahul; Duncan, Gordon S.; Cescon, David W.; Silvester, Jennifer; Chu, Mandy; Hodgson, Kate; Berger, Thorsten; Wakeham, Andrew; Palomero, Luís; García-Valero, Mar; Pujana, Miguel Ángel; Mak, Tak W.; McGaha, Tracy L.; Cappello, Paola; Gorrini, Chiara

doi:10.1073/pnas.1819473116

Cited by 152 publications

(105 citation statements)

References 62 publications

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“…However, the transient oxidative stress can generate ligands that activate anti-inflammatory signaling systems such as Peroxisome Proliferator-Activated Receptor-gamma (PPARγ) and Liver X-Receptor-alpha (LXRα) in monocyte-macrophages during training [ 63 ]. In addition, ROS modulate macrophages’ immunosuppressive phenotype through the up-regulation of programmed death-ligand 1 (PD-L1) [ 64 ]. Thus, more ROS production at the beginning of the race training may enhance the creation of the anti-inflammatory state.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses

Witkowska-Piłaszewicz

Pingwara

Winnicka

2020

Antioxidants

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Physical activity has an influence on a variety of processes in an athlete’s organism including the immune system. Unfortunately, there is a lack of studies regarding racehorse immune cells, especially when the horse model is compared to human exercise physiology. The aim of the study was to determine changes in immune cell proliferation, lymphocyte populations, and monocyte functionality in trained and untrained racehorses after exercise. In this study, field data were collected. The cells from 28 racehorses (14 untrained and 14 well-trained) were collected before and after exercise (800 m at a speed of about 800 m/min) and cultured for 4 days. The expression of CD4, CD8, FoxP3, CD14, MHCII, and CD5 in PBMC, and reactive oxygen species (ROS) production, as well as cell proliferation, were evaluated by flow cytometry. In addition, IL-1β, IL-4, IL-6, IL-10, IL-17, INF-γ, and TNF-α concentrations were evaluated by ELISA. The creation of an anti-inflammatory environment in well-trained horses was confirmed. In contrast, a pro-inflammatory reaction occurred in untrained horses after training. In conclusion, an anti-inflammatory state occurs in well-trained racehorses, which is an adaptational reaction to an increased workload during training.

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Section: Discussionmentioning

confidence: 99%

The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses

Witkowska-Piłaszewicz

Pingwara

Winnicka

2020

Antioxidants

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“…IHC analysis of clinical specimens confirmed the positive correlation of NOX4 and CD68 or CD206 [253]. ROS accumulation in BMDMs that was reached by ROS inducer, glutathione synthesis inhibitor buthionine sulphoximine (BSO), results in increased expression of programmed death ligand-1 (PD-L1) and production of IL-10, IL-17, IL-4, IL-1b, insulin-like growth factor-binding protein 3 (IGFBP-3), and chemokine (C-X-C motif) ligand 1 (CXCL1) that are associated with an immune-suppressive phenotype of macrophages [271].…”

Section: Role Of Hypoxiamentioning

confidence: 99%

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Larionova

Kazakova

Patysheva

et al. 2020

Cancers

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Macrophages are key innate immune cells in the tumor microenvironment (TME) that regulate primary tumor growth, vascularization, metastatic spread and tumor response to various types of therapies. The present review highlights the mechanisms of macrophage programming in tumor microenvironments that act on the transcriptional, epigenetic and metabolic levels. We summarize the latest knowledge on the types of transcriptional factors and epigenetic enzymes that control the direction of macrophage functional polarization and their pro- and anti-tumor activities. We also focus on the major types of metabolic programs of macrophages (glycolysis and fatty acid oxidation), and their interaction with cancer cells and complex TME. We have discussed how the regulation of macrophage polarization on the transcriptional, epigenetic and metabolic levels can be used for the efficient therapeutic manipulation of macrophage functions in cancer.

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“…Hence, inhibition of TAM-derived angiogenesis-inducing factors potentially improve the efficacy of chemotherapy [119,120]. Recent study, regarding immune checkpoint blockad with chemotherapy in TNBC patients, reactive oxygen species (ROS) and oxidative stress induced by taxane in macrophages render them immunosuppressive and expressing PD-L1 [121].…”

Section: Induction Of Treatment Resistance By Tamsmentioning

confidence: 99%

Role of Tumor-Associated Myeloid Cells in Breast Cancer

Jin

Koo

2020

Cells

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Stromal immune cells constitute the tumor microenvironment. These immune cell subsets include myeloid cells, the so-called tumor-associated myeloid cells (TAMCs), which are of two types: tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Breast tumors, particularly those in human epidermal growth factor receptor 2 (HER-2)-positive breast cancer and triple-negative breast cancer, are solid tumors containing immune cell stroma. TAMCs drive breast cancer progression via immune mediated, nonimmune-mediated, and metabolic interactions, thus serving as a potential therapeutic target for breast cancer. TAMC-associated breast cancer treatment approaches potentially involve the inhibition of TAM recruitment, modulation of TAM polarization/differentiation, reduction of TAM products, elimination of MDSCs, and reduction of MDSC products. Furthermore, TAMCs can enhance or restore immune responses during cancer immunotherapy. This review describes the role of TAMs and MDSCs in breast cancer and elucidates the clinical implications of TAMs and MDSCs as potential targets for breast cancer treatment.

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Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1

Cited by 152 publications

References 62 publications

The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses

The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Role of Tumor-Associated Myeloid Cells in Breast Cancer

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