Evidence map›Paper›PMID 40696153›Full record

Trial reportNature cancer2025

Combination of pembrolizumab and radiotherapy induces systemic antitumor immune responses in immunologically cold non-small cell lung cancer.

Justin Huang, Willemijn S M E Theelen, Zineb Belcaid, Mimi Najjar, Daphne van der Geest, Dipika Singh, Christopher Cherry, Archana Balan, James R White, Jaime Wehr and 7 more

2 registry-linked trialsAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 47 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 3 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.

NCT02492568 phase2completednot on this map

Randomized Phase II, 2-arm Study of Pembrolizumab After High Dose Radiation (SBRT) Versus Pembrolizumab Alone in Patients With Advanced Non-small Cell Lung Cancer

TypeinterventionalSponsorThe Netherlands Cancer InstituteRan2015 to 2018Enrolled92ConditionsNon-Small Cell Lung CancerArmspembrolizumab, Stereotactic Body Radiation Therapy
NCT07756190 phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Phase II Study of Radscopal Radiotherapy Combined With Immunotherapy as First-Line Treatment for Chemotherapy-Ineligible Patients With De Novo Metastatic Nasopharyngeal Carcinoma

TypeinterventionalSponsorSun Yat-sen UniversityRan2026 to 2030Enrolled28ConditionsNasopharyngeal Carcinoma (NPC), Metastatic Nasopharyngeal CarcinomaArmsSintilimab, ipilimumab, Radscopal Radiotherapy
3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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  10. SARS-CoV-2 mRNA Vaccination Improved Survival in NSCLC Treated With Radiotherapy.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
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  12. Radiation oncology at a new frontier: Hotspots, challenges, and emerging advances.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026
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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.

Justin Huang *The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Willemijn S M E Theelen *Netherlands Cancer Institute, Amsterdam, The Netherlands.
Zineb Belcaid *The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mimi NajjarThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Daphne van der GeestNetherlands Cancer Institute, Amsterdam, The Netherlands.
Dipika SinghThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christopher CherryThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Archana BalanThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
James R WhiteThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jaime WehrThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rachel KarchinThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-5069-1239
Noushin NiknafsThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michel M van den HeuvelDepartment of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Victor E VelculescuThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-1195-438X
Kellie N SmithThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-6295-8930
Paul BaasNetherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-7018-9556
Valsamo AnagnostouThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. vanagno1@jhmi.edu.ORCID http://orcid.org/0000-0001-9480-3047

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
ECOG-ACRIN Thoracic Malignancies Integrated Translational Science CenterUG1CA233259 · NCI · EMORY UNIVERSITY · PI CARBONE, DAVID P., LEAL, TICIANA · 2019 to 2025
$5.1M
Large-Scale Genetic Analyses of Human CancerR01CA121113 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANAGNOSTOU, VALSAMO, VELCULESCU, VICTOR E. · 2006 to 2022
$4.3M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA121113NCI NIH HHS UG1 CA233259U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA006973U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA121113U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA233259
6 · The paper itself

Abstract

The abscopal effects of radiation may sensitize immunologically cold tumors to immune checkpoint inhibition. We investigated the immunostimulatory effects of radiotherapy leveraging multiomic analyses of serial tissue and blood biospecimens (n = 293) from a phase 2 clinical trial of stereotactic body radiation therapy (SBRT) followed by pembrolizumab in metastatic non-small cell lung cancer ( NCT02492568 ). Participants with immunologically cold tumors (low tumor mutation burden, null programmed death ligand 1 expression or Wnt pathway mutations) had significantly longer progression-free survival in the SBRT arm. Induction of interferon-γ, interferon-α and antigen processing and presentation gene sets was significantly enriched after SBRT in nonirradiated tumor sites. Significant on-therapy expansions of new and pre-existing T cell clones in both the tumor (abscopal) and the blood (systemic) compartments were noted alongside clonal neoantigen-reactive autologous T cell responses in participants with long-term survival after radioimmunotherapy. These findings support the systemic immunomodulatory and antitumor effects of radioimmunotherapy and may open a therapeutic window of opportunity to overcome immunotherapy resistance.

Indexed as

Antibodies, Monoclonal, HumanizedCarcinoma, Non-Small-Cell LungLung NeoplasmsAgedCombined Modality TherapyFemaleHumansMaleMiddle AgedRadioimmunotherapyRadiosurgeryT-LymphocytesAntibodies, Monoclonal, Humanizedpembrolizumab

Identifiers

PMID40696153
PMCPMC12559004

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.