CD47 Blockade Inhibits Tumor Progression through Promoting Phagocytosis of Tumor Cells by M2 Polarized Macrophages in Endometrial Cancer

Gu, Sheng-Lan; Ni, Ting; Wang, Jing; Liu, Yao; Fan, Qiong; Wang, Yiwei; Huang, Ting; Chu, Yiwei; Sun, Xiaojiang; Wang, Yudong

doi:10.1155/2018/6156757

Cited by 61 publications

(41 citation statements)

References 43 publications

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“…123109, clone BM8) for 30 minutes at 4°C and washed with 2% FBS in PBS for flow cytometry assay with FACSCalibur (BD Bioscience). The phagocytic activity was calculated as the percentage of CFSE + macrophages …”

Section: Methodsmentioning

confidence: 99%

miR‐378a Modulates Macrophage Phagocytosis and Differentiation through Targeting CD47‐SIRPα Axis in Atherosclerosis

Chen

Wang

et al. 2019

Scand J Immunol

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Background: Signal regulatory protein alpha (SIRPa) is an essential signalling molecule that modulates inflammatory responses in macrophages. However, the regulation of SIRPs and its dynamic changes in macrophages under inflammatory stimulation in atherosclerosis remain uncertain. Objective: The study aimed to identify the miRNAs that regulate SIRPa transcription and their roles in modulating phagocytosis, differentiation and cholesterol efflux in macrophages. Methods: ApoE knockout mice were fed with a high-fat diet for 12 weeks. Intimal lesion areas and lipid accumulation were assessed by haematoxylin and eosin (HE) and oil red O staining. The expression of mRNAs/miRNAs was assessed by RNAseq (RNA sequencing) and RT-qPCR (real-time quantitative polymerase chain reaction). The identification of miR-378a associated with SIRPa regulation in macrophages induced by ox-LDL was confirmed by RT-qPCR and Western blot.The phagocytosis and differentiation of macrophages were detected to figure out the role of miR-378a and SIRPa. Results: SIRPa was proved to be a target of miR-378a. Reduced miR-378a can promote the expression of SIRPa. RNA-seq data showed that the levels of mRNA associated with macrophage phenotypes and SIRPa-CD47 axis were increasing significantly with a decreasing phagocytic phenotype in ApoE −/− mice vs wild-type (WT) mice (P < 0.01). The level of miR-378a was reduced in the aorta of ApoE −/− mice vs WT mice. The experiment in vitro showed that overexpression of miR-378a in macrophages decreased the level of Sirpa mRNA obviously vs control (P < 0.01).The phagocytic activity of miR-378a-transfected macrophages was promoted vs control (P < 0.05). miR-378a significantly depleted Sirpa levels in oxidized lowdensity lipoprotein (ox-LDL)-stimulated macrophages (P < 0.05), and depletion of miR-378a reversed Sirpa reduction obviously (P < 0.05). miR-378a promoted the secretion of TNF-a and IL-6 indirectly. Conclusion: It has been demonstrated that miR-378a regulates SIRPa-mediated phagocytosis and polarization of macrophages by a direct or indirect way. This 2 of 10 | CHEN Et al. research may provide a new path to promote reverse cholesterol transport of macrophages and hinder the progress of atherosclerosis.

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Section: Methodsmentioning

confidence: 99%

miR‐378a Modulates Macrophage Phagocytosis and Differentiation through Targeting CD47‐SIRPα Axis in Atherosclerosis

Chen

Wang

et al. 2019

Scand J Immunol

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“…Substantial evidence has been provided that overexpression of CD47 by many cancer types is an important mechanism of resistance to phagocytosis [138]. The pharmacological inhibition of CD47 restored phagocytosis and killing of tumor cells by macrophages in various preclinical cancer models, resulting in effective anti-tumor immune responses [139][140][141]. Combination therapies have the potential to increase this efficacy.…”

Section: Antibodies To Reprogram Tamsmentioning

confidence: 99%

Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses

Anfray

Ummarino

Andón

et al. 2019

Cells

206

183

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: Established evidence demonstrates that tumor-infiltrating myeloid cells promote rather than stop-cancer progression. Tumor-associated macrophages (TAMs) are abundantly present at tumor sites, and here they support cancer proliferation and distant spreading, as well as contribute to an immune-suppressive milieu. Their pro-tumor activities hamper the response of cancer patients to conventional therapies, such as chemotherapy or radiotherapy, and also to immunotherapies based on checkpoint inhibition. Active research frontlines of the last years have investigated novel therapeutic strategies aimed at depleting TAMs and/or at reprogramming their tumor-promoting effects, with the goal of re-establishing a favorable immunological anti-tumor response within the tumor tissue. In recent years, numerous clinical trials have included pharmacological strategies to target TAMs alone or in combination with other therapies. This review summarizes the past and current knowledge available on experimental tumor models and human clinical studies targeting TAMs for cancer treatment.

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“…The signal regulatory protein-α (SIRPα, also known as SHPS1), expressed on the surface of phagocytic cells, such as macrophages, interacts with CD47, expressed by the target cells, resulting in the inhibition of phagocytosis and thus acting as a “don’t eat me” signal for tissue homeostasis [ 152 ]. In preclinical cancer models, the pharmacological inhibition of CD47, overexpressed by cancer cells, restores the ability of macrophages to phagocyte and kill tumor cells [ 153 , 154 , 155 ]. Antibodies able to inhibit SIRPα showed satisfactory antitumoral activity in lung cancer models, however their effect was limited in time [ 156 ].…”

Section: Monoclonal Antibodies To Reprogram Tamsmentioning

confidence: 99%

Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing

Belgiovine

Digifico

Anfray

et al. 2020

JCM

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In the last decade, it has been well-established that tumor-infiltrating myeloid cells fuel not only the process of carcinogenesis through cancer-related inflammation mechanisms, but also tumor progression, invasion, and metastasis. In particular, tumor-associated macrophages (TAMs) are the most abundant leucocyte subset in many cancers and play a major role in the creation of a protective niche for tumor cells. Their ability to generate an immune-suppressive environment is crucial to escape the immune system and to allow the tumor to proliferate and metastasize to distant sites. Conventional therapies, including chemotherapy and radiotherapy, are often not able to limit cancer growth due to the presence of pro-tumoral TAMs; these are also responsible for the failure of novel immunotherapies based on immune-checkpoint inhibition. Several novel therapeutic strategies have been implemented to deplete TAMs; however, more recent approaches aim to use TAMs themselves as weapons to fight cancer. Exploiting their functional plasticity, the reprogramming of TAMs aims to convert immunosuppressive and pro-tumoral macrophages into immunostimulatory and anti-tumor cytotoxic effector cells. This shift eventually leads to the reconstitution of a reactive immune landscape able to destroy the tumor. In this review, we summarize the current knowledge on strategies able to reprogram TAMs with single as well as combination therapies.

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CD47 Blockade Inhibits Tumor Progression through Promoting Phagocytosis of Tumor Cells by M2 Polarized Macrophages in Endometrial Cancer

Cited by 61 publications

References 43 publications

miR‐378a Modulates Macrophage Phagocytosis and Differentiation through Targeting CD47‐SIRPα Axis in Atherosclerosis

miR‐378a Modulates Macrophage Phagocytosis and Differentiation through Targeting CD47‐SIRPα Axis in Atherosclerosis

Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses

Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing

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