Macrophages in radiation injury: a new therapeutic target

Meziani, Lydia; Deutsch, Éric; Mondini, Michele

doi:10.1080/2162402x.2018.1494488

Cited by 66 publications

(47 citation statements)

References 28 publications

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“…This includes the bystander effect (when the signals from irradiated cells affect neighboring non-irradiated tissue responses) [51,61,85,86,87]. An example is the direct IR effect on the activation of macrophages, which then produce bystander signals and play an important role in the development of radiation injury [88]. An abscopal effect, defined as “an action at a distance from the irradiated volume but within the same organism” is also observed [70,85,89,90,91,92,93].…”

Section: Tumor Milieu As a Critical Immune Mediator Of Rtmentioning

confidence: 99%

“…CAFs are metabolically active, secrete SASP (senescence-associated secretory phenotype) factors (growth factors, proteases, inflammatory mediators, or extracellular matrix proteins) and regulate tumor growth [127,131]. In addition, high doses of IR (>8 Gy) may promote the anti-inflammatory activation of macrophages [88], and a dose of 20 Gy activates the M2 phenotype of TAM with tolerogenic properties by induction of immune inhibitory molecules COX-2/PGE2 and NO [127,132].…”

Section: Different Responses Of the Tme After Various Doses Of Rtmentioning

confidence: 99%

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Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

Jarosz-Biej

Smolarczyk

Cichoń

et al. 2019

IJMS

374

259

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Radiotherapy (RT), besides cancer cells, also affects the tumor microenvironment (TME): tumor blood vessels and cells of the immune system. It damages endothelial cells and causes radiation-induced inflammation. Damaged vessels inhibit the infiltration of CD8+ T lymphocytes into tumors, and immunosuppressive pathways are activated. They lead to the accumulation of radioresistant suppressor cells, including tumor-associated macrophages (TAMs) with the M2 phenotype, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). The area of tumor hypoxia increases. Hypoxia reduces oxygen-dependent DNA damage and weakens the anti-cancer RT effect. It activates the formation of new blood vessels and leads to cancer relapse after irradiation. Irradiation may also activate the immune response through immunogenic cell death induction. This leads to the “in situ” vaccination effect. In this article, we review how changes in the TME affect radiation-induced anticancer efficacy. There is a very delicate balance between the activation of the immune system and the immunosuppression induced by RT. The effects of RT doses on immune system reactions and also on tumor vascularization remain unclear. A better understanding of these interactions will contribute to the optimization of RT treatment, which may prevent the recurrence of cancer.

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Section: Tumor Milieu As a Critical Immune Mediator Of Rtmentioning

confidence: 99%

Section: Different Responses Of the Tme After Various Doses Of Rtmentioning

confidence: 99%

Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

Jarosz-Biej

Smolarczyk

Cichoń

et al. 2019

IJMS

374

259

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“…rt enhances the antitumor effect of Duox1 −/− proinflammatory macrophages Macrophages are key players in the responses of tumors to radiotherapy and exert either antitumor or protumor effects according to their phenotype. 15 Subsets of macrophages with an immunosuppressive/anti-inflammatory phenotype can limit the efficacy of RT. 16 17 We demonstrated that DUOX1 reduced the proinflammatory properties of macrophages in vitro (figure 1), and we therefore hypothesized that DUOX1 could be involved in macrophage-mediated mechanisms of resistance to RT.…”

Section: Duox1 Decreases the Antitumor Effect Of Proinflammatory Macrmentioning

confidence: 99%

Dual oxidase 1 limits the IFNγ-associated antitumor effect of macrophages

Meziani

Thoré

Hamon

et al. 2020

J Immunother Cancer

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BackgroundMacrophages play pivotal roles in tumor progression and the response to anticancer therapies, including radiotherapy (RT). Dual oxidase (DUOX) 1 is a transmembrane enzyme that plays a critical role in oxidant generation.MethodsSince we found DUOX1 expression in macrophages from human lung samples exposed to ionizing radiation, we aimed to assess the involvement of DUOX1 in macrophage activation and the role of these macrophages in tumor development.ResultsUsing Duox1−/− mice, we demonstrated that the lack of DUOX1 in proinflammatory macrophages improved the antitumor effect of these cells. Furthermore, intratumoral injection of Duox1−/− proinflammatory macrophages significantly enhanced the antitumor effect of RT. Mechanistically, DUOX1 deficiency increased the production of proinflammatory cytokines (IFNγ, CXCL9, CCL3 and TNFα) by activated macrophages in vitro and the expression of major histocompatibility complex class II in the membranes of macrophages. We also demonstrated that DUOX1 was involved in the phagocytotic function of macrophages in vitro and in vivo. The antitumor effect of Duox1−/− macrophages was associated with a significant increase in IFNγ production by both lymphoid and myeloid immune cells.ConclusionsOur data indicate that DUOX1 is a new target for macrophage reprogramming and suggest that DUOX1 inhibition in macrophages combined with RT is a new therapeutic strategy for the management of cancers.

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“…Melatonin can attenuate the activity of macrophages [29]. As macrophage activity plays a key role in the release of pro-fibrotic cytokines such as TGF-β, IL-4, IL-10, and IL-13, melatonin may have a beneficial effect in the prevention of the late effects of ionizing radiation through modulation and maintenance of macrophages [30]. Apoptosis and senescence are important types of cell death following exposure to radiation that may be involved in the infiltration of macrophages to irradiated tissues [31].…”

Section: Discussionmentioning

confidence: 99%

Radiation-Induced Dual Oxidase Upregulation in Rat Heart Tissues: Protective Effect of Melatonin

et al. 2019

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Background: Radiation-induced heart injury can lead to increased risk of heart failure, attack, and ischemia. Some studies proposed IL-4 and IL-13 as two important cytokines that are involved in late effects of ionizing radiation. On the other hand, these cytokines may, through upregulation of Duox1 and Duox2, induce chronic oxidative stress, inflammation, and fibrosis. In this study, we evaluated the upregulation of Duox1 and Duox2 pathways in hearts following chest irradiation in rats and then detected possible attenuation of them by melatonin. Materials and Methods: Twenty male Wistar rats were divided into four groups: (1) control; (2) melatonin treated (100 mg/kg); (3) radiation (15 Gy gamma rays); (4) melatonin treated before irradiation. All rats were sacrificed after 10 weeks and their heart tissues collected for real-time PCR (RT-PCR), ELISA detection of IL-4 and IL-13, as well as histopathological evaluation of macrophages and lymphocytes infiltration. Results: Results showed an upregulation of IL-4, IL4ra1, Duox1, and Duox2. The biggest changes were for IL4ra1 and Duox1. Treatment with melatonin before irradiation could attenuate the upregulation of all genes. Melatonin also caused a reduction in IL-4 as well as reverse infiltration of inflammatory cells. Conclusion: Duox1 and Duox2 may be involved in the late effects of radiation-induced heart injury. Also, via attenuation of these genes, melatonin can offer protection against the toxic effects of radiation on the heart.

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Macrophages in radiation injury: a new therapeutic target

Cited by 66 publications

References 28 publications

Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

Dual oxidase 1 limits the IFNγ-associated antitumor effect of macrophages

Radiation-Induced Dual Oxidase Upregulation in Rat Heart Tissues: Protective Effect of Melatonin

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