Evidence map›Paper›PMID 42009646›Full record

ArticleNature communications2026

Chemotherapy-induced activation of caspase-1 and IL-1α release by cancer cells remotely skews myelopoiesis to drive pro tumorigenic systemic neutrophil-dominant inflammation.

Stephen Qr Wong, Kazukuni Hayashi, Ethan J Subel, Yung Hsing Huang, Hongbo Gao, Haley E Garcia, Sophie J Porter, Mustafa Karabicici, Xen Ping Hoi, Mark D Alonzo and 18 more

Abstract read
In one paragraph

Article in Nature communications, 2026. 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. NINJ1: implications for plasma membrane rupture and disease.Biochemical Society transactions · 2026
    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

28 authors.

Stephen Qr Wong *Department of Urology, Houston Methodist Research Institute, Houston, TX, USA.ORCID 0000-0002-8906-6465
Kazukuni Hayashi *Department of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-0325-3719
Ethan J Subel *Department of Urology, Houston Methodist Research Institute, Houston, TX, USA.ORCID 0009-0008-3728-4680
Yung Hsing HuangDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.ORCID 0000-0002-8200-961X
Hongbo GaoDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.
Haley E GarciaDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.
Sophie J PorterDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.
Mustafa KarabiciciDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.
Xen Ping HoiDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.ORCID 0000-0001-7610-7291
Mark D AlonzoDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.
Armine KasabyanDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.
Efrosini TsoukoBaylor College of Medicine, Houston, TX, USA.
Crystal S ShinBaylor College of Medicine, Houston, TX, USA.
Lisa Bouchier-HayesBaylor College of Medicine, Houston, TX, USA.ORCID 0000-0003-3886-5977
Dimitrios KorentzelosDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Chen ChenDepartment of Pathology, Houston Methodist Research Institute, Houston, TX, USA.
Michael BrooksDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.
Zheng YinMethodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA.ORCID 0000-0002-3547-0606
Renil S TitusDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.
Lan ZhouMethodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA.
Yinan GongDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.ORCID 0000-0002-3643-4682
Yulin LiMethodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA.ORCID 0000-0003-3479-9909
Stephen Tc WongMethodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA.ORCID 0000-0001-9188-6502
Ziad El-ZaatariDepartment of Pathology, Houston Methodist Research Institute, Houston, TX, USA.
Dharam KaushikDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.
Raj SatkunasivamDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.
Fotis NikolosDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA.ORCID 0000-0002-8622-0017
Keith S ChanDepartment of Urology, Houston Methodist Research Institute, Houston, TX, USA. kschan@houstonmethodist.org.

Funding

The stromal microenvironment as a co-organizer of bladder carcinogenesis and progressionU54CA274375 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI Simon Knott · 2022 to 2026
$10.2M
Targeting tumor repopulation and the immune microenvironment to overcome chemoresistanceR01CA255609 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI CHAN, KEITH SYSON · 2021 to 2025
$2.2M
Regulation of inhibitory DAMP to harness immunogenic cell deathF31CA247257 · NCI · CEDARS-SINAI MEDICAL CENTER · PI HAYASHI, KAZUKUNI · 2020 to 2022
$116k
NCI NIH HHS F31 CA247257NCI NIH HHS R01 CA255609NCI NIH HHS U54 CA274375U.S. Department of Defense (United States Department of Defense) CA200750
6 · The paper itself

Abstract

While chemotherapy-induced tumor cell death is known to modulate the local immune landscape, its systemic impact on distant bone marrow-a site essential for immune cell maturation-remains underexplored. Here, we show that gemcitabine chemotherapy induces inflammatory caspase-1-dependent pyroptosis in epithelial cancer cells (epiCaspase-1). Despite its inflammatory nature, epiCaspase-1-mediated cell death is non-immunogenic. Clinically, elevated expression of an epiCaspase-1 gene signature correlates with worse patient outcomes. Mechanistically, epiCaspase-1 triggers the noncanonical release of IL-1α through NINJ1 lytic pores, remotely skewing bone marrow hematopoiesis towards granulocyte-monocyte progenitors and mature neutrophil output. This systemic reprogramming elevates the neutrophil-to-lymphocyte ratio (NLR) in both peripheral blood and the local tumor microenvironment. Pharmacological inhibition of caspase-1 and IL-1α disrupts this cascade, normalizes hematopoiesis, and recalibrates NLR by promoting intratumoral CD8

Indexed as

Caspase 1InflammationInterleukin-1alphaMyelopoiesisNeutrophilsAnimalsCarcinogenesisCD8-Positive T-LymphocytesCell Line, TumorFemaleHumansMicePyroptosisTumor MicroenvironmentCaspase 1IL1A protein, humanInterleukin-1alpha

Identifiers

PMID42009646
PMCPMC13216336

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.