Twist and miR-34a Are Involved in the Generation of  Tumor-Educated Myeloid-Derived Suppressor Cells

Wang, Xin; Chang, Xusheng; Zhuo, Guangzuan; Sun, Mingxia; Yin, Kai

doi:10.3390/ijms141020459

Cited by 15 publications

(18 citation statements)

References 74 publications

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“…Of relevance, the tumor-suppressing microRNA miR34a, a target of p53, has been shown to be crucially involved in regulating the expansion of MDSCs. 34 In the present study we demonstrate that patients with AML exhibit increased presence of MDSCs in their peripheral blood in comparison with normal controls. Of note, we demonstrate that MDSCs in patients with AML may be derived from leukemic or apparently normal progenitor populations, suggesting an effect of the tumor on the surrounding myeloid populations irrespective of their clonal derivation.…”

Section: Introductionsupporting

confidence: 58%

MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia

Pyzer¹,

Stroopinsky²,

Rajabi

et al. 2017

Blood

143

118

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Myeloid-derived suppressor cells (MDSCs) play a critical role in promoting immune tolerance and disease growth. The mechanism by which tumor cells evoke the expansion of MDSCs in acute myeloid leukemia (AML) has not been well described. We have demonstrated that patients with AML exhibit increased presence of MDSCs in their peripheral blood, in comparison with normal controls. Cytogenetic studies demonstrated that MDSCs in patients with AML may be derived from leukemic or apparently normal progenitors. Engraftment of C57BL/6 mice with TIB-49 AML led to an expansion of CD11b Gr1 MDSCs in bone marrow and spleen. Coculture of the AML cell lines MOLM-4, THP-1 or primary AML cells with donor peripheral blood mononuclear cells elicited a cell contact-dependent expansion of MDSCs. MDSCs were suppressive of autologous T-cell responses as evidenced by reduced T-cell proliferation and a switch from a Th1 to a Th2 phenotype. We hypothesized that the expansion of MDSCs in AML is accomplished by tumor-derived extracellular vesicles (EVs). Using tracking studies, we demonstrated that AML EVs are taken-up myeloid progenitor cells, resulting in the selective proliferation of MDSCs in comparison with functionally competent antigen-presenting cells. The MUC1 oncoprotein was subsequently identified as the critical driver of EV-mediated MDSC expansion. MUC1 induces increased expression of c-myc in EVs that induces proliferation in the target MDSC population via downstream effects on cell cycle proteins. Moreover, we demonstrate that the microRNA miR34a acts as the regulatory mechanism by which MUC1 drives c-myc expression in AML cells and EVs.

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Section: Introductionsupporting

confidence: 58%

MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia

Pyzer¹,

Stroopinsky²,

Rajabi

et al. 2017

Blood

143

118

View full text Add to dashboard Cite

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“…MiR-155 and miR-21 promote the expansion of functional MDSCs (12). Twist basic helix-loop-helix transcription factor and miR-34a participate in the generation of tumor-induced MDSCs (13). MiR-34a expands MDSCs via apoptosis inhibition (14).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA expression profiles of granulocytic myeloid-derived suppressor cells from mice bearing Lewis lung carcinoma

Jiang

Gao

Hao

et al. 2016

Molecular Medicine Reports

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Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that can suppress antitumor immunity. MDSCs are divided into granulocytic (G-MDSCs) and monocytic subsets. In the present study, the microRNA profiles of the G-MDSCs were determined and the differential expression of microRNAs between G-MDSCs from tumor-bearing mice and tumor-free mice was examined. The number of G-MDSCs in spleens of Lewis lung carcinoma (LLC)-bearing mice was ~6-fold higher than in spleens of normal mice (13.54±1.74% vs. 2.14±1.44%; P<0.01) and G-MDSCs account for about 72.9% of all MDSCs. The microRNA (miRNA) profiles of the G-MDSCs from spleen of LLC-bearing mice were obtained using a microRNA microarray and compared with their counterparts from spleens of tumor-free mice. A total of 43 miRNAs with >1.3-fold increased or decreased change were differentially expressed between the experimental and control group mice. The levels of nine of these differentially expressed miRNAs, miRNA-468 (miR-486), miR-192, miR-128, miR-125a, miR-149, miR-27a, miR-125b, miR-350 and miR-328, were also analyzed by RT-qPCR to validate the microarray data. The concordance rate between the results tested by the two methods was 88.9%. Bioinformatics analyses revealed that these miRNAs may act on various target genes, including Adar, Pik3r1, Rybp and Rabgap1, to regulate the survival, differentiation and the function of tumor-induced granulocytic MDSCs. The results revealed microRNAs and potential targets that may be vital for regulating survival, differentiation and function of G-MDSCs induced by LLC. Further investigation should be performed to clarify the roles of these microRNAs in regulating LLC-induced granulocytic MDSCs and the target genes that mediate their functions.

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“…In one study, overexpression of Twist in cancer cell lines was associated with an expansion of murine MDSCs in cocultured myeloid precursor cells. Conversely, siRNA silencing of Twist expression partly abrogated the expansion of MDSCs in this model …”

Section: Factors Involved In the Expansion Of Mdscs In Cancermentioning

confidence: 78%

“…MiR34a targets p53 and has been linked to the expansion of MDSCs. The combination of Twist silencing and MiR34a overexpression nearly completely abrogated the expansion of MDSCs …”

Section: Micrornas Involved In Mdsc Expansionmentioning

confidence: 99%

Myeloid‐derived suppressor cells as effectors of immune suppression in cancer

Pyzer

Cole

Rosenblatt

et al. 2016

Intl Journal of Cancer

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The tumor microenvironment consists of an immunosuppressive niche created by the complex interactions between cancer cells and surrounding stromal cells. A critical component of this environment are myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immature myeloid cells arrested at different stages of differentiation and expanded in response to a variety of tumor factors. MDSCs exert diverse effects in modulating the interactions between immune effector cells and the malignant cells. An increased presence of MDSCs is associated with tumor progression, poorer outcomes, and decreased effectiveness of immunotherapeutic strategies. In this article, we will review our current understanding of the mechanisms that underlie MDSC expansion and their immune-suppressive function. Finally, we review the preclinical studies and clinical trials that have attempted to target MDSCs, in order to improve responses to cancer therapies.

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Twist and miR-34a Are Involved in the Generation of Tumor-Educated Myeloid-Derived Suppressor Cells

Cited by 15 publications

References 74 publications

MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia

MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia

MicroRNA expression profiles of granulocytic myeloid-derived suppressor cells from mice bearing Lewis lung carcinoma

Myeloid‐derived suppressor cells as effectors of immune suppression in cancer

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