Evidence map›Paper›PMID 41314982›Full record

Observational studyJournal for immunotherapy of cancer2025

Immune-modulating effects on tumor-draining lymph nodes of neoadjuvant chemoradiotherapy combined with dual immunotherapy in patients with T3-4N0-2 NSCLC.

Ezgi B Ulas, Sofie J I Koomen, Anne Vrijmoet, Ilias Houda, H Ibrahim Korkmaz, Chris Dickhoff, Idris Bahce, Suresh Senan, Tanja D de Gruijl, Marieke F Fransen and 3 more

Abstract readObservational Study
In one paragraph

Observational study in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Review
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

13 authors.

Ezgi B UlasDepartment of Pulmonary Medicine, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-1551-738X
Sofie J I KoomenCancer Center Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-7699-7669
Anne VrijmoetDepartment of Pathology, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.
Ilias HoudaDepartment of Pulmonary Medicine, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.
H Ibrahim KorkmazAmsterdam institute for Immunology and Infectious diseases, Amsterdam, The Netherlands.
Chris DickhoffCancer Center Amsterdam, Amsterdam, The Netherlands.
Idris BahceDepartment of Pulmonary Medicine, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-1111-608X
Suresh SenanCancer Center Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-3995-2204
Tanja D de GruijlCancer Center Amsterdam, Amsterdam, The Netherlands.
Marieke F FransenDepartment of Pulmonary Medicine, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-3036-8618
Teodora RadonicCancer Center Amsterdam, Amsterdam, The Netherlands.
Febe van MaldegemCancer Center Amsterdam, Amsterdam, The Netherlands f.vanmaldegem@amsterdamumc.nl.ORCID http://orcid.org/0000-0002-2544-544X
Famke L SchneidersCancer Center Amsterdam, Amsterdam, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTumor-draining lymph nodes (TDLN) play a key role in inducing and promoting antitumor immunity. TDLN are commonly situated near the primary tumor and are therefore often exposed to therapeutic radiation. The impact of induction therapies comprising concurrent immunotherapy and radiation on TDLN is poorly understood. We studied the immune-modulating effects in TDLN of patients with T3-4N0-2 non-small cell lung cancer (NSCLC) using a combination of spatial transcriptomics and immunohistochemical analyses.

methodsThis observational cohort study collected TDLN from 2 groups: (1) patients from the INCREASE trial who were treated with neoadjuvant ipilimumab/nivolumab (IPI/NIVO) plus chemoradiotherapy (CRT) (n=25) and (2) a matched control cohort of patients with NSCLC who had neoadjuvant CRT only (n=25). TDLN were classified based on the cumulative dose of radiation received, categorized as low (≤5 Gy), intermediate (20-30 Gy), or high dose (50-60 Gy). The TDLN were subjected to duplex immunohistochemistry of CD8/Ki67, PD-1/FOXP3, and CD8/cleaved caspase-3. On a subset of TDLN, additional GeoMx spatial transcriptomics profiling of CD8/Ki67+T cell hotspots was carried out.

resultsAfter addition of IPI/NIVO to CRT in the INCREASE cohort, resected TDLN showed robust type I immune responses and increased levels of CD8 and regulatory T cells in irradiated TDLN when compared with the control cohort. These immune responses were observed across all radiation dose groups, with the most pronounced effects in high dose TDLN. Significant changes in extracellular matrix and macrophage-associated gene signatures, indicating elevated fibrosis and prolonged inflammation, were observed in the TDLN with high radiation exposure, changes which were partially alleviated by immunotherapy.

conclusionIn the INCREASE trial, neoadjuvant IPI/NIVO combined with CRT for patients with T3-4N0-2 NSCLC elicited enhanced immune responses in TDLN despite exposure to high dose radiation. Even though radiation-induced fibrosis was evident in high dose TDLN, the immune responses were not diminished when compared with low dose TDLN. These findings underscore the resilience of TDLN immunological function under intense radiation exposure.

Indexed as

Carcinoma, Non-Small-Cell LungChemoradiotherapyImmunotherapyLung NeoplasmsLymph NodesNeoadjuvant TherapyAgedFemaleHumansMaleMiddle AgedImmune Checkpoint InhibitorLung CancerNeoadjuvantRadiotherapy/radioimmunotherapy

Identifiers

PMID41314982
PMCPMC12684110

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.