Evidence map›Paper›PMID 27001312›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016

B7-H4(B7x)-Mediated Cross-talk between Glioma-Initiating Cells and Macrophages via the IL6/JAK/STAT3 Pathway Lead to Poor Prognosis in Glioma Patients.

Yu Yao, Hongxing Ye, Zengxin Qi, Lianjie Mo, Qi Yue, Aparajita Baral, Dave S B Hoon, Juan Carlos Vera, John D Heiss, Clark C Chen and 6 more

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

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 2 pooled it
7.8field-weighted citation impact, top 2% 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

121 citing papers in PubMed, 2 syntheses or guidelines pooled it, 193 citations in OpenAlex.

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  18. Reactive Astrocytes in Glioma: Emerging Opportunities and Challenges.International journal of molecular sciences · 2025
    Review
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  20. Article

61 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

16 authors at 2 institutions in 1 country.

Yu Yao *Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Hongxing Ye *Department of Neurosurgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R China.
Zengxin Qi *Shanghai Medical College, Fudan University, Shanghai 200032, China.
Lianjie Mo *Department of Neurosurgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
Qi YueShanghai Medical College, Fudan University, Shanghai 200032, China.
Aparajita BaralDepartment of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 437001, China.
Dave S B HoonDept Molecular Oncology, John Wayne Cancer Institute, Santa Monica, Ca 90404, USA.
Juan Carlos VeraSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, 10/3D20, MSC-1414, Bethesda, Maryland 20892-1414, USA.
John D HeissSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, 10/3D20, MSC-1414, Bethesda, Maryland 20892-1414, USA.
Clark C ChenCenter for Theoretic and Applied Oncology, University of California, San Diego, CA 92093, USA.
Jianmin ZhangSchool of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R China.
Kunlin JinDepartment of Pharmacology, University of North Texas Health Science Center, Fort Worth, TX76107, USA.
Ying WangDepartment of Neuropathology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Xingxing ZangDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, NY 10461, USA.
Ying MaoDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Liangfu ZhouDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Huashan Hospital · CNFudan University · CN

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI THOMAS E ROHAN · 1985 to 2026
$111.2M
Molecular Pathogenesis of NeoplasiaZIANS003052 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI HEISS, JOHN · 2009 to 2025
$20.7M
Tumor-expressed immune checkpoint B7x-mediated resistance to anti-CTLA-4 therapy.R01CA175495 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI ZANG, XINGXING · 2014 to 2025
$5.1M
Mechanisms and Therapies of B7x and B7-H3 in T1DR01DK100525 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI ZANG, XINGXING · 2015 to 2019
$1.9M
Targeting Mechanisms of Acquired Temozolomide Resistance in GlioblastomaR01NS097649 · NINDS · UNIVERSITY OF MINNESOTA · PI CHEN, CLARK CHIN-CHUNG · 2016 to 2021
$1.7M
NCI NIH HHS P30 CA013330NCI NIH HHS R01 CA175495NIDDK NIH HHS R01 DK100525NINDS NIH HHS R01 NS097649
6 · The paper itself

Abstract

purposeThe objective of this study was to evaluate clinical significance and immunosuppressive mechanisms of B7-H4 (B7x/B7S1), a B7 family member, in glioma. EXPERIMENTAL

designB7-H4 levels in glioma tissue/cerebral spinal fluid (CSF) were compared between different grades of glioma patients. Survival data were analyzed with Kaplan-Meier to determine the prognostic value of B7-H4. Cytokines from CD133(+) cells to stimulate the expression of B7-H4 on human macrophages (Mφs) were investigated by FACS, neutralizing antibodies, and Transwell chemotaxis assay. shRNA, reporter vector, and chromatin immunoprecipitation were used to determine the binding of STAT3 to the B7-H4 promoter. The function of B7-H4(+) Mφs in vitro was evaluated through phagocytosis, T-cell proliferation/apoptosis, and cytokine production as well as in the xenografted model for in vivo analysis.

resultsWe found that B7-H4 expression in tumors was associated with prognosis of human glioblastoma and correlated directly with malignant grades. Mechanistically, glioma initiating CD133(+) cells and Mφs/microglia cointeraction activated expression of B7-H4 via IL6 and IL10 in both tumor cells and microenvironment supporting cells. IL6-activated STAT3 bound to the promoter of B7-H4 gene and enhanced B7-H4 expression. Furthermore, CD133(+) cells mediated immunosuppression through B7-H4 expression on Mφs/microglia by silencing of B7-H4 expression on these cells, which led to increased microenvironment T-cell function and tumor regression in the xenograft glioma mouse model.

conclusionsWe have identified B7-H4 activation on Mφs/microglia in the microenvironment of gliomas as an important immunosuppressive event blocking effective T-cell immune responses. Clin Cancer Res; 22(11); 2778-90. ©2016 AACR.

Indexed as

AdolescentAdultAgedAnimalsBrain NeoplasmsCell Line, TumorFemaleGlioblastomaHumansInterleukin-6Janus KinasesKaplan-Meier EstimateLymphocyte ActivationMacrophagesMaleMice, Inbred C57BLIL6 protein, humanInterleukin-6Janus KinasesSTAT3 protein, humanSTAT3 Transcription FactorV-Set Domain-Containing T-Cell Activation Inhibitor 1VTCN1 protein, human

Identifiers

PMID27001312
PMCPMC4891287
OpenAlexW2308813426

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.