Evidence map›Paper›PMID 41879666›Full record

ArticleThe Journal of experimental medicine2026

Local gene editing of fibroblasts in tumors reveals a new cancer-associated fibroblast state.

Nicholas F Kuhn, Itzia Zaleta-Linares, Kenneth H Hu, Tristan Courau, Brittany Davidson, Tammie Tam, Chih-Wei Chu, Maxime J Kinet, Michael D Rosenblum, Alexis J Combes and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Nicholas F KuhnDepartment of Pathology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5634-0846
Itzia Zaleta-LinaresDepartment of Pathology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0009-0001-1637-271X
Kenneth H HuDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-0294-0202
Tristan CourauDepartment of Pathology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-1819-9516
Brittany DavidsonDepartment of Pathology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3538-2822
Tammie TamDepartment of Pathology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0009-0006-2245-1226
Chih-Wei ChuDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0009-0004-9529-5928
Maxime J KinetDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-9026-8777
Michael D RosenblumDepartment of Dermatology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-0462-5732
Alexis J CombesDepartment of Pathology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-9110-6542
William A NybergDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-9982-1305
Justin EyquemBakar ImmunoX Initiative, University of California, San Francisco , San Francisco, CA, USA.ORCID 0000-0001-8262-1190
Matthew F KrummelDepartment of Pathology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-7915-3533

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VAISSE, CHRISTIAN · 2003 to 2019
$21.8M
The Tumor Microenvironment Niche of Type I conventional Dendritic CellsR01CA197363 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MATTHEW F KRUMMEL · 2017 to 2026
$4.5M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
Cancer Research Institute CRI4546NCI NIH HHS R01 CA197363NIDDK NIH HHS P30 DK063720NIH HHS 1S10OD028511-01NIH HHS P30 DK063720NIH HHS R01CA197363NIH HHS S10 OD028511Parker Institute for Cancer Immunotherapy C-02350Parker Institute for Cancer Immunotherapy C-04189University of California, San Francisco
6 · The paper itself

Abstract

Fibroblasts play critical roles in regulating cellular relationships during tissue homeostasis, immunity, and tumor biology at multiple sites. However, tools to perturb fibroblasts at just one site in vivo are limited, restricting our understanding of how these cellular relationships act locally. We optimized local gene editing of fibroblasts in mouse tumor models to investigate how fibroblast perturbations affect the tumor microenvironment (TME). By knocking out receptors Osmr, Tgfbr2, or Il1r1 on cancer-associated fibroblasts (CAFs), we uncover that TGFBR2 signaling loss induces the emergence of a new Col18a1hi CAF cell state that is associated with worse survival in pancreatic cancer patients. Combinatorial gene KOs in CAFs reveals a circuit where these Col18a1hi CAFs reshape the TME by recruiting Siglec-Fhi neutrophils via Cxcl5 expression, and where this Col18a1hi CAF cell state is dependent on TNFR1 and canonical Wnt signaling. Together, a fast, affordable, and modular engineering method is demonstrated, allowing discovery of modified fibroblast identities and local intercellular relationships in the TME.

Indexed as

Cancer-Associated FibroblastsGene EditingPancreatic NeoplasmsAnimalsHumansMiceReceptor, Transforming Growth Factor-beta Type IITumor MicroenvironmentReceptor, Transforming Growth Factor-beta Type II

Identifiers

PMID41879666
PMCPMC13668321

What OpenQuestion holds

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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 OpenQuestion graph.