Evidence map›Paper›PMID 27358487›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2017

Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas.

Jennifer E Kim, Mira A Patel, Antonella Mangraviti, Eileen S Kim, Debebe Theodros, Esteban Velarde, Ann Liu, Eric W Sankey, Ada Tam, Haiying Xu and 16 more

Open access · greenAbstract 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, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 303 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
303citing papers in PubMed, 3 pooled it
18.0field-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

303 citing papers in PubMed, 3 syntheses or guidelines pooled it, 459 citations in OpenAlex.

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  15. Immune checkpoint TIM-3 in tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026
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243 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

26 authors at 2 institutions in 1 country.

Jennifer E KimDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Mira A PatelDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Antonella MangravitiDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Eileen S KimDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Debebe TheodrosDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Esteban VelardeDepartment of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland.
Ann LiuDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Eric W SankeyDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Ada TamFlow Cytometry Core, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
Haiying XuDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland.
Dimitrios MathiosDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Christopher M JacksonDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Sarah Harris-BookmanDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Tomas Garzon-MuvdiDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Mary SheuDepartment of Dermatology, Johns Hopkins University, Baltimore, Maryland.
Allison M MartinDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Betty M TylerDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Phuoc T TranDepartment of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland.
Xiaobu YeDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Alessandro OliviDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Janis M TaubeDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland.
Peter C BurgerDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Charles G DrakeDepartment of Oncology, Johns Hopkins University, Baltimore, Maryland.
Henry BremDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Drew M PardollDepartment of Oncology, Johns Hopkins University, Baltimore, Maryland.
Michael LimDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland. mlim3@jhmi.edu.
Johns Hopkins University · USSidney Kimmel Comprehensive Cancer Center · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
Structure-Functions Studies of Twist1-induced Radioresistance in Lung CancerR01CA166348 · NCI · JOHNS HOPKINS UNIVERSITY · PI TRAN, PHUOC T. · 2013 to 2017
$1.7M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA166348NIGMS NIH HHS T32 GM136577
6 · The paper itself

Abstract

purposeCheckpoint molecules like programmed death-1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM-3) are negative immune regulators that may be upregulated in the setting of glioblastoma multiforme. Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produce long-term survivors in a murine glioma model. However, tumor-infiltrating lymphocytes (TIL) can express multiple checkpoints, and expression of ≥2 checkpoints corresponds to a more exhausted T-cell phenotype. We investigate TIM-3 expression in a glioma model and the antitumor efficacy of TIM-3 blockade alone and in combination with anti-PD-1 and SRS. EXPERIMENTAL

designC57BL/6 mice were implanted with murine glioma cell line GL261-luc2 and randomized into 8 treatment arms: (i) control, (ii) SRS, (iii) anti-PD-1 antibody, (iv) anti-TIM-3 antibody, (v) anti-PD-1 + SRS, (vi) anti-TIM-3 + SRS, (vii) anti-PD-1 + anti-TIM-3, and (viii) anti-PD-1 + anti-TIM-3 + SRS. Survival and immune activation were assessed.

resultsDual therapy with anti-TIM-3 antibody + SRS or anti-TIM-3 + anti-PD-1 improved survival compared with anti-TIM-3 antibody alone. Triple therapy resulted in 100% overall survival (P < 0.05), a significant improvement compared with other arms. Long-term survivors demonstrated increased immune cell infiltration and activity and immune memory. Finally, positive staining for TIM-3 was detected in 7 of 8 human GBM samples.

conclusionsThis is the first preclinical investigation on the effects of dual PD-1 and TIM-3 blockade with radiation. We also demonstrate the presence of TIM-3 in human glioblastoma multiforme and provide preclinical evidence for a novel treatment combination that can potentially result in long-term glioma survival and constitutes a novel immunotherapeutic strategy for the treatment of glioblastoma multiforme. Clin Cancer Res; 23(1); 124-36. ©2016 AACR.

Indexed as

RadiosurgeryAnimalsAntineoplastic Agents, ImmunologicalBiomarkersCombined Modality TherapyDisease Models, AnimalFemaleGliomaHepatitis A Virus Cellular Receptor 2HumansImmunologic MemoryImmunophenotypingLymphocytesLymphocytes, Tumor-InfiltratingMiceMolecular Targeted TherapyAntineoplastic Agents, ImmunologicalBiomarkersHavcr2 protein, mouseHepatitis A Virus Cellular Receptor 2Programmed Cell Death 1 Receptor

Identifiers

PMID27358487
PMCPMC5735836
OpenAlexW2463645998

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.