MIR-708 promotes phagocytosis to eradicate T-ALL cells by targeting CD47

Huang, Wei; Wang, Wen-Tao; Fang, Ke; Chen, Zhenhua; Sun, Yu-Meng; Han, Cai; Sun, Lin-Yu; Luo, Xue-Qun; Chen, Yue‐Qin

doi:10.1186/s12943-018-0768-2

Cited by 48 publications

(41 citation statements)

References 10 publications

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“…43 Besides, P21waf1 has been reported to upregulate CD47 expression in LSA74T colorectal cells and MCF7 breast cells; 44 miR-708 could directly target CD47 through binding to 3′UTR and was inversely correlated with CD47 expression in acute lymphoblastic leukemia tumor cells. 45 Our study showed that TAM-derived IL-6 upregulated CD47 expression on hepatoma cells via the STAT3 pathway and that inhibition of IL-6 signaling by neutralizing antibody or STAT3 phosphorylation could antagonize the effect of TAM-induced CD47 expression and the anti-phagocytotic capacity of tumor cells. A recent report showed that CD47 expression could be regulated by TNF-αinduced nuclear factor kappa B (NF-κB) activation on hepatoma cells.…”

Section: Discussionmentioning

confidence: 62%

Macrophages induce CD47 upregulation via IL-6 and correlate with poor survival in hepatocellular carcinoma patients

Chen

Zheng

et al. 2019

OncoImmunology

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CD47 is known to be involved in phagocyte-mediated tumor clearance; however, its expression, clinical significance, and regulatory mechanism in hepatocellular carcinoma (HCC) remain poorly understood. In the present study, we found that upregulation of CD47 expression on tumor cells was correlated with poor overall survival and recurrence-free survival in patients with HCC. Abundance of macrophages (Mφs) infiltration was found in CD47 + tumor tissues. Mechanistic studies revealed that IL-6 derived from tumorinfiltrating Mφs could upregulate CD47 expression on hepatoma cells through activation of the STAT3 pathway. Neutralization of CD47 or disruption of the IL-6-STAT3 axis reduced the ability of tumor cells to escape phagocytosis. Moreover, CD47 blockade could enhance Mφ-mediated phagocytosis in the presence of chemotherapeutic drugs, and HCC patients with lower CD47 expression were more likely to benefit from adjuvant transcatheter arterial chemoembolization (TACE) treatment. These findings revealed that Mφderived IL-6 was responsible for CD47 expression on hepatoma cells, which might be served as a potential prognostic marker and a predictor for patients who might benefit from adjuvant TACE treatment.

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Section: Discussionmentioning

confidence: 62%

Macrophages induce CD47 upregulation via IL-6 and correlate with poor survival in hepatocellular carcinoma patients

Chen

Zheng

et al. 2019

OncoImmunology

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“…19 In addition to treatment with antibodies, the modulation of upstream factors can suppress the Sirpα/CD47 axis. Some studies have shown how CD47 expression is upregulated in cancer cells, 20,21 whereas the regulatory mechanism underlying Sirpα expression in TAMs is still not clear. Thus, we aimed to examine the expression profile of Sirpα in TAMs and to further identify the upstream transcription factors of Sirpα.…”

Section: Introductionmentioning

confidence: 99%

The Ap-2α/Elk-1 axis regulates Sirpα-dependent tumor phagocytosis by tumor-associated macrophages in colorectal cancer

Wang

Luo

Chen

et al. 2020

Sig Transduct Target Ther

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The inhibitory receptor signal regulatory protein-α (Sirpα) is a myeloid-specific immune checkpoint that engages the "don't eat me" signal CD47, which is expressed on tumor and normal tissue cells. However, the profile and regulatory mechanism of Sirpα expression in tumor-associated macrophages (TAMs) are still not clear. Here, we found that the expression of Sirpα in TAMs increased dynamically with colorectal cancer (CRC) progression. Mechanistically, CRC cell-derived lactate induced the nuclear translocation of the transcription factor Ap-2α from the cytoplasm in TAMs. Ap-2α functioned as a transcription factor for Elk-1 by binding to the conserved element GCCTGC located at −1396/−1391 in the mouse Elk-1 promoter. Subsequently, the Elk-1 protein bound to two conserved sites, CTTCCTACA (located at −229/−221) and CTTCCTCTC (located at −190/−182), in the mouse Sirpα promoter and promoted Sirpα expression in TAMs. Functionally, the macrophage-specific knockout of Ap-2α notably promoted the phagocytic activity of TAMs and suppressed CRC progression, whereas these effects were prevented by the transgenic macrophage-specific expression of Elk-1, which regulated TAM phagocytosis and CRC development in a Sirpα-dependent manner. Furthermore, we showed that Elk-1 expression was positively correlated with Sirpα expression in TAMs and was associated with poor survival in CRC patients. Taken together, our findings revealed a novel mechanism through which CRC evades innate immune surveillance and provided potential targets for macrophage-based immunotherapy for CRC patients.Signal Transduction and Targeted Therapy (2020) 5:35; https://doi.

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“…This may be related to an abnormal decrease in several miRNA molecules, which are often negative regulators of tumour cell genes. The expression of miRNAs that regulate the "Don't Eat Me" signal could be a target of new anti‐tumour therapies for this immune checkpoint . Based on the CD47‐SIRPα pathway, researchers have used nanotechnology to create a nanocage composed of human ferritin containing a SIRPα variant in such a way as to display multiple SIRPα molecules on the surface of the cage.…”

Section: Anti‐cancer Mechanisms For Targeting Mhc Class I‐lilrb1mentioning

confidence: 99%

“…miR‐133a has been found to promote phagocytosis to eradicate oesophageal squamous cell carcinoma cells by directly targeting the 3' UTR of CD47 mRNA . miR‐708 regulates CD47 expression and is a novel prognostic marker in T cell acute lymphoblastic leukaemia . At present, miRNA‐125a is the only known miRNA that can negatively regulate MHC class I expression on oesophageal adenocarcinoma cells .…”

Section: Mhc Class I and Mirnasmentioning

confidence: 99%

The MHC class I‐LILRB1 signalling axis as a promising target in cancer therapy

et al. 2019

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Immune checkpoint inhibitors are among the newest, cutting-edge methods for the treatment of cancer. Currently, they primarily influence T cell adaptive immunotherapy targeting the PD-1/PD-L1 and CTLA-4/B7 signalling pathways. These inhibitors fight cancer by reactivating the patient's own adaptive immune system, with good results in many cancers. With the discovery of the "Don't Eat Me" molecule, CD47, antibody-based drugs that target the macrophage-related innate immunosuppressive signalling pathway, CD47-SIRPα, have been developed and have achieved stunning results in the laboratory and the clinic, but there remain unexplained instances of tumour immune escape. While investigating the immunological tolerance of cancer to anti-CD47 antibodies, a second "Don't Eat Me" molecule on tumour cells, beta 2 microglobulin (β2m), a component of MHC class I, was described. Some tumour cells reduce their surface expression of MHC class I to escape T cell recognition.However, other tumour cells highly express β2m complexed with the MHC class I heavy chain to send a "Don't Eat Me" signal by binding to leucocyte immunoglobulin-like receptor family B, member 1 (LILRB1) on macrophages, leading to a loss of immune surveillance. Investigating the mechanisms underlying this immunosuppressive MHC class I-LILRB1 signalling axis in tumour-associated macrophages will be useful in developing therapies to restore macrophage function and control MHC class I signalling in patient tumours. The goal is to promote adaptive immunity while suppressing the innate immune response to tumours. This work will identify new therapeutic targets for the development of pharmaceutical-based tumour immunotherapy.

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MIR-708 promotes phagocytosis to eradicate T-ALL cells by targeting CD47

Cited by 48 publications

References 10 publications

Macrophages induce CD47 upregulation via IL-6 and correlate with poor survival in hepatocellular carcinoma patients

Macrophages induce CD47 upregulation via IL-6 and correlate with poor survival in hepatocellular carcinoma patients

The Ap-2α/Elk-1 axis regulates Sirpα-dependent tumor phagocytosis by tumor-associated macrophages in colorectal cancer

The MHC class I‐LILRB1 signalling axis as a promising target in cancer therapy

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