Evidence map›Paper›PMID 29540832›Full record

ArticleOncogene2018

miR-21 depletion in macrophages promotes tumoricidal polarization and enhances PD-1 immunotherapy.

Jiajia Xi, Qian Huang, Lei Wang, Xiaodong Ma, Qipan Deng, Munish Kumar, Zhiyuan Zhou, Ling Li, Zhaoyang Zeng, Ken H Young and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 2 pooled it
5.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 126 citations in OpenAlex.

  1. miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review.International journal of molecular sciences · 2024
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  10. Do Metastatic Cells Arise from PD-L1International journal of molecular sciences · 2026
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26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Jiajia XiDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Qian HuangDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Lei WangInstitute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, 510631, China.
Xiaodong MaDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Qipan DengDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Munish KumarDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Zhiyuan ZhouDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Ling LiDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, 450000, China.
Zhaoyang ZengCancer Research Institute, Central South University, Changsha, 410078, China.
Ken H YoungDepartments of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
Mingzhi ZhangDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, 450000, China.
Yong LiDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. liy2@ccf.org.ORCID http://orcid.org/0000-0001-8838-1714
Cleveland Clinic Lerner College of Medicine · USFirst Affiliated Hospital of Zhengzhou University · CNSouth China Normal University · CNCentral South University · CNThe University of Texas MD Anderson Cancer Center · USUniversity of Allahabad · IN

Funding

Convergence of MicroRNAs and p53 Signaling in Multiple Myeloma: Environmental CoR01CA138688 · NCI · UNIVERSITY OF LOUISVILLE · PI LI, YONG · 2009 to 2017
$2.9M
Modulation of MicroRNAs with Xenobiotics to Target c-MycR01CA177810 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LI, YONG · 2015 to 2019
$1.8M
NCI NIH HHS R01 CA138688NCI NIH HHS R01 CA177810
6 · The paper itself

Abstract

MicroRNA-21 (miR-21) is one of the most abundant microRNAs in mammalian cells. It has been intensively studied for its role in regulating apoptosis and oncogenic transformation. However, the impact of miR-21 on host anti-tumor immunity remains unknown. Tumor-associated macrophages are a major leukocyte type that infiltrates tumors and predominantly develops into immunosuppressive, tumor-promoting M2-like macrophages. In contrast, the pro-inflammatory M1-like macrophages have tumoricidal activity. In this study, we show that genetic deficiency of miR-21 promotes the polarization of macrophages toward an M1-like phenotype in vivo and in vitro in the presence of tumor cells; thus it confers host mice with enhanced anti-tumor immunity. By downregulating JAK2 and STAT1, miR-21 inhibits the IFN-γ-induced STAT1 signaling pathway, which is required for macrophage M1 polarization. We also show that the expression of miR-21 in macrophages is regulated upon polarization stimuli as well as upon macrophages co-culturing with tumor cells. Thus, tumor cells may stimulate miR-21 expression in tumor-associated macrophages to prevent tumoricidal M1 polarization. However, augmented STAT1 signaling mediated by miR-21 deficiency upregulates PD-L1 expression in macrophages, which is known to inhibit phagocytic anti-tumor activity. This adverse effect can be alleviated by PD-1 blockade; indeed, miR-21 depletion in macrophages and PD-1 antibody treatment offer superior anti-tumor activity than either agent alone. These studies shed lights on potential application of the combination of miR-21 inhibition and immune checkpoint blockade to target the tumor microenvironment.

Indexed as

AnimalsAntibodies, MonoclonalB7-H1 AntigenCell PolarityGene Expression Regulation, NeoplasticHumansImmunotherapyInterferon-gammaJanus Kinase 2MacrophagesMice, KnockoutMicroRNAsProgrammed Cell Death 1 ReceptorSTAT1 Transcription FactorSurvival RateXenograft Model Antitumor AssaysAntibodies, MonoclonalB7-H1 AntigenCd274 protein, mouseInterferon-gammaJak2 protein, mouseJanus Kinase 2MicroRNAsMIRN21 microRNA, humanMIRN21 microRNA, mousePdcd1 protein, mouseProgrammed Cell Death 1 ReceptorStat1 protein, mouseSTAT1 Transcription Factor

Identifiers

PMID29540832
PMCPMC5993583
OpenAlexW2792705680

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.