Evidence map›Paper›PMID 26014097›Full record

ArticleCancer immunology research2015

Resistance to Antiangiogenic Therapy Is Associated with an Immunosuppressive Tumor Microenvironment in Metastatic Renal Cell Carcinoma.

Xian-De Liu, Anh Hoang, Lijun Zhou, Sarathi Kalra, Alper Yetil, Mianen Sun, Zhiyong Ding, Xuesong Zhang, Shanshan Bai, Peter German and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

124 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
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  13. CircRNAAutophagy · 2025
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64 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

23 authors.

Xian-De LiuDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Anh HoangDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Lijun ZhouDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sarathi KalraDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Alper YetilDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Mianen SunDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Zhiyong DingDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Xuesong ZhangDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Shanshan BaiDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Peter GermanDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Pheroze TamboliDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Priya RaoDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jose A KaramDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Christopher WoodDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Surena MatinDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Amado ZuritaDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Axel BexDepartment of Urology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Arjan W GriffioenDepartment of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
Jianjun GaoDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Padmanee SharmaDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Nizar TannirDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Kanishka SircarDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Eric JonaschDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. ejonasch@mdanderson.org.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
NCI NIH HHS CA016672NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

Renal cell carcinoma (RCC) is an immunogenic and proangiogenic cancer, and antiangiogenic therapy is the current mainstay of treatment. Patients with RCC develop innate or adaptive resistance to antiangiogenic therapy. There is a need to identify biomarkers that predict therapeutic resistance and guide combination therapy. We assessed the interaction between antiangiogenic therapy and the tumor immune microenvironment and determined their impact on clinical outcome. We found that antiangiogenic therapy-treated RCC primary tumors showed increased infiltration of CD4(+) and CD8(+) T lymphocytes, which was inversely related to patient overall survival and progression-free survival. Furthermore, specimens from patients treated with antiangiogenic therapy showed higher infiltration of CD4(+)FOXP3(+) regulatory T cells and enhanced expression of checkpoint ligand programed death-ligand 1 (PD-L1). Both immunosuppressive features were correlated with T-lymphocyte infiltration and were negatively related to patient survival. Treatment of RCC cell lines and RCC xenografts in immunodeficient mice with sunitinib also increased tumor PD-L1 expression. Results from this study indicate that antiangiogenic treatment may both positively and negatively regulate the tumor immune microenvironment. These findings generate hypotheses on resistance mechanisms to antiangiogenic therapy and will guide the development of combination therapy with PD-1/PD-L1-blocking agents.

Indexed as

Angiogenesis InhibitorsAnimalsAntineoplastic AgentsB7-H1 AntigenBevacizumabBiomarkers, TumorCarcinoma, Renal CellCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDrug Resistance, NeoplasmHeterograftsHumansImmune ToleranceIndolesKidney NeoplasmsLymphocytes, Tumor-InfiltratingAngiogenesis InhibitorsAntineoplastic AgentsB7-H1 AntigenBevacizumabBiomarkers, TumorCD274 protein, humanIndolesPyrrolesSunitinib

Identifiers

PMID26014097
PMCPMC4561186

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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.