Evidence map›Paper›PMID 31025274›Full record

ArticleJournal of neuro-oncology2019

Combination anti-CXCR4 and anti-PD-1 immunotherapy provides survival benefit in glioblastoma through immune cell modulation of tumor microenvironment.

Adela Wu, Russell Maxwell, Yuanxuan Xia, Pina Cardarelli, Miho Oyasu, Zineb Belcaid, Eileen Kim, Alice Hung, Andrew S Luksik, Tomas Garzon-Muvdi and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
13.1field-weighted citation impact, top 1% 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

90 citing papers in PubMed, 142 citations in OpenAlex.

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30 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

17 authors at 3 institutions in 1 country.

Adela WuDepartment of Neurosurgery, Stanford Health Care, Stanford, CA, 94304, USA.ORCID http://orcid.org/0000-0003-4543-9300
Russell MaxwellDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
Yuanxuan XiaDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
Pina CardarelliBristol-Myers Squibb, New York, NY, USA.
Miho OyasuBristol-Myers Squibb, New York, NY, USA.
Zineb BelcaidDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
Eileen KimDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
Alice HungDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
Andrew S LuksikDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
Tomas Garzon-MuvdiDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
Christopher M JacksonDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
Dimitrios MathiosDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
Debebe TheodrosDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
John CogswellBristol-Myers Squibb, New York, NY, USA.
Henry BremDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
Drew M PardollDepartment of Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
Michael LimDepartment of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, 21205, USA. mlim3@jhmi.edu.
Johns Hopkins Hospital · USBristol-Myers Squibb (United States) · USStanford Health Care · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEmerging evidence suggests that myeloid cells play a critical role in glioblastoma (GBM) immunosuppression. Disappointing results of recent checkpoint inhibitor trials suggest that combination immunotherapy with alternative agents could be fruitful in overcoming immunosuppression. Overexpression of chemokine receptor CXCR4 is associated with poor prognosis in GBM. We investigate the treatment effects of combination immunotherapy with anti-PD-1 and anti-CXCR4 in a murine glioma model.

methodsC57BL/6 mice were implanted with GL261-Luc+ glioma cells and randomized into 4 arms: (1) control (2) anti-PD-1 (3) anti-CXCR4, and (4) anti-PD-1 and anti-CXCR4 therapy. Overall survival and median survival were assessed. Cell populations were assessed by flow cytometry.

resultsCombination therapy conferred a significant survival benefit compared to control and monotherapy arms. Mice that received combination therapy demonstrated immune memory and decreased populations of immunosuppressive tumor-infiltrating leukocytes, such as monocytic myeloid-derived suppressor cells and microglia within the brain. Furthermore, combination therapy improved CD4+/CD8+ ratios in the brain as well as contributed to increased levels of pro-inflammatory cytokines.

conclusionsAnti-CXCR4 and anti-PD-1 combination immunotherapy modulates tumor-infiltrating populations of the glioma microenvironment. Targeting myeloid cells with anti-CXCR4 facilitates anti-PD-1 to promote an antitumor immune response and improved survival rates.

Indexed as

ImmunotherapyAnimalsAntineoplastic Agents, ImmunologicalBrain NeoplasmsCytokinesFemaleGlioblastomaHumansMiceMice, Inbred C57BLMyeloid CellsProgrammed Cell Death 1 ReceptorReceptors, CXCR4Survival RateTumor MicroenvironmentXenograft Model Antitumor AssaysAntineoplastic Agents, ImmunologicalCXCR4 protein, mouseCytokinesPdcd1 protein, mouseProgrammed Cell Death 1 ReceptorReceptors, CXCR4Checkpoint inhibitorCXCR4GliomaImmunotherapyPD-1

Identifiers

PMID31025274
OpenAlexW2941630943

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.