Evidence map›Paper›PMID 40038278›Full record

ArticleNature communications2025

PARP inhibitor radiosensitization enhances anti-PD-L1 immunotherapy through stabilizing chemokine mRNA in small cell lung cancer.

Xiaozhuo Ran, Bell Xi Wu, Venkatasubramanian Vidhyasagar, Lifang Song, Xu Zhang, Reese Jalal Ladak, Mona Teng, Wail Ba-Alawi, Vivek Philip, Housheng H He and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

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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

12 authors.

Xiaozhuo RanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Bell Xi WuPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Venkatasubramanian VidhyasagarPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Lifang SongPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Xu ZhangRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada.
Reese Jalal LadakRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada.
Mona TengPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Wail Ba-AlawiPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Vivek PhilipPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Housheng H HePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-2898-3363
Nahum SonenbergRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-4707-8759
Benjamin H LokPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. benjamin.lok@uhn.ca.ORCID http://orcid.org/0000-0002-3675-8847

Funding

Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
Clinical and Translational Science CenterUL1TR000457 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI IMPERATO-MCGINLEY, JULIANNE L · 2012 to 2016
$46.0M
Understanding the molecular mechanism of a protein-recycling complex in small cell lung cancer treatment resistance.U01CA253383 · NCI · UNIVERSITY HEALTH NETWORK · PI LOK, BENJAMIN H, RAUGHT, BRIAN · 2020 to 2025
$1.4M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) U01CA253383NCATS NIH HHS UL1 TR000457NCATS NIH HHS UL1 TR001873NCI NIH HHS U01 CA253383Terry Fox Research Institute (Institut de Recherche Terry Fox) TFRI Project #1124
6 · The paper itself

Abstract

Immunotherapy (IO) is an effective treatment for various cancers; however, the benefits are modest for small cell lung cancer (SCLC). The poor response of SCLC to anti-PD-1/PD-L1 IO is due in part to the lack of cytotoxic T cells because of limited chemokine expression from SCLC tumors. Immunogenic radiosensitizers that enhance chemokine expression may be a promising strategy forward. Here, we show that the PARP inhibitors (PARPi), including olaparib, talazoparib and veliparib, in combination with radiotherapy (RT) enhance the immune activation and anti-tumor efficacy in SCLC cell lines, patient-derived xenograft (PDX) and syngeneic mouse models. The effect is further enhanced by continued delivery of adjuvant PARPi. The combination treatment (PARPi with RT) activates the cGAS-STING pathway and increases the mRNA levels of the T cell chemo-attractants CCL5 and CXCL10. In addition to upregulation of transcription, the combination treatment increases chemokine CXCL10 protein levels via stabilization of CXCL10 mRNA in an EIF4E2-dependent manner. The incorporation of anti-PD-L1 IO into the PARPi with RT combination therapy further improves the anti-tumor efficacy by increasing T cell infiltration and function. This study thus provides a proof of principle for the combination of PARP inhibitors, RT and anti-PD-L1 IO as a treatment strategy for SCLC.

Indexed as

B7-H1 AntigenChemokinesImmunotherapyLung NeoplasmsPoly(ADP-ribose) Polymerase InhibitorsRadiation-Sensitizing AgentsSmall Cell Lung CarcinomaAnimalsBenzimidazolesCell Line, TumorChemokine CCL5Chemokine CXCL10FemaleHumansImmune Checkpoint InhibitorsMiceB7-H1 AntigenBenzimidazolesCCL5 protein, humanCD274 protein, humanChemokine CCL5Chemokine CXCL10ChemokinesCXCL10 protein, humanImmune Checkpoint InhibitorsolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsRadiation-Sensitizing AgentsRNA, Messengerveliparib

Identifiers

PMID40038278
PMCPMC11880360

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.