Evidence map›Paper›PMID 25527358›Full record

ArticleCancer immunology research2015

Stereotactic Radiation Therapy Augments Antigen-Specific PD-1-Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen.

Andrew B Sharabi, Christopher J Nirschl, Christina M Kochel, Thomas R Nirschl, Brian J Francica, Esteban Velarde, Theodore L Deweese, Charles G Drake

Registry-linked trialOpen access · bronzeAbstract readEvaluation Study
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. It is linked to trial NCT03971214 (Pilot Study on PD-1 Inhibitors Consolidation After Standard First-line Chemotherapy and Radiotherapy in Extensive-stage Small Cell Lung Cancer), which is not on this map. Cited by 406 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
406citing papers in PubMed, 4 pooled it
16.4field-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.

NCT03971214 phase1unknown statusnot on this mapstarted 2019, after this paper: background citation

Pilot Study on PD-1 Inhibitors Consolidation After Standard First-line Chemotherapy and Radiotherapy in Extensive-stage Small Cell Lung Cancer

TypeinterventionalSponsorChinese Academy of Medical SciencesRan2019 to 2021Enrolled6ConditionsExtensive-stage Small Cell Lung Cancer, Radiotherapy, ImmunotherapyArmsPD-1 inhibitor JS-001
3 · Its place in the literature

Who cites it

406 citing papers in PubMed, 4 syntheses or guidelines pooled it, 638 citations in OpenAlex.

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  16. Sequential Immune Activation of Effector T Cells as Biomarkers of Response to Durvalumab in Patients with Locally Advanced NSCLC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Observational
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346 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Andrew B SharabiDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Christopher J NirschlDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Christina M KochelDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Thomas R NirschlDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Brian J FrancicaDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Esteban VelardeDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Theodore L DeweeseDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Charles G DrakeDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland. cdrake@jhmi.edu.
Johns Hopkins University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
CELLULAR &MOLECULAR MECH OF INFLAMMATORY REACTIONST32AI007247 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Joel L Pomerantz · 1985 to 2026
$10.2M
Role of Tc17 cells in tumor immunotherapyR01CA154555 · NCI · JOHNS HOPKINS UNIVERSITY · PI PARDOLL, DREW M. · 2012 to 2016
$1.7M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA154555NIAID NIH HHS T32 AI007247
6 · The paper itself

Abstract

The immune-modulating effects of radiotherapy (XRT) have gained considerable interest recently, and there have been multiple reports of synergy between XRT and immunotherapy. However, additional preclinical studies are needed to demonstrate the antigen-specific nature of radiation-induced immune responses and elucidate potential mechanisms of synergy with immunotherapy. Here, we demonstrate the ability of stereotactic XRT to induce endogenous antigen-specific immune responses when it is combined with anti-PD-1 checkpoint blockade immunotherapy. Using the small animal radiation research platform (SARRP), image-guided stereotactic XRT delivered to B16-OVA melanoma or 4T1-HA breast carcinoma tumors resulted in the development of antigen-specific T cell- and B cell-mediated immune responses. These immune-stimulating effects of XRT were significantly increased when XRT was combined with either anti-PD-1 therapy or regulatory T cell (Treg) depletion, resulting in improved local tumor control. Phenotypic analyses of antigen-specific CD8 T cells revealed that XRT increased the percentage of antigen-experienced T cells and effector memory T cells. Mechanistically, we found that XRT upregulates tumor-associated antigen-MHC complexes, enhances antigen cross-presentation in the draining lymph node, and increases T-cell infiltration into tumors. These findings demonstrate the ability of XRT to prime an endogenous antigen-specific immune response and provide an additional mechanistic rationale for combining radiation with PD-1 blockade in the clinic.

Indexed as

AnimalsAntigen PresentationAntigens, NeoplasmCD8-Positive T-LymphocytesCell Line, TumorCombined Modality TherapyCross-PrimingFemaleImmunologic MemoryImmunotherapyLymphocytes, Tumor-InfiltratingMammary Neoplasms, ExperimentalMelanoma, ExperimentalMice, KnockoutProgrammed Cell Death 1 ReceptorRadiosurgeryAntigens, NeoplasmPdcd1 protein, mouseProgrammed Cell Death 1 Receptor

Identifiers

PMID25527358
PMCPMC4390444
OpenAlexW2022208959

What OpenQuestion holds

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Registered trials

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.