Association of tumor Schwann cells with epithelial-mesenchymal transition and immune-suppressive microenvironment in triple-negative breast cancer.
Overview
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center,Buffalo, NY 14263 USA
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine,Yokohama, Kanagawa Japan
- Department of Breast and Endocrine Surgery, Yokohama City University Graduate School of Medicine,Yokohama, Kanagawa Japan
- Department of Breast and Thyroid Surgery, Yokohama City University Medical Center,Yokohama, Kanagawa Japan
- Department of Medicine, Winship Cancer Institute of Emory University,Atlanta, GA USA
- Department of Immunology, Roswell Park Comprehensive Cancer Center,Buffalo, NY USA
- Department of Breast Surgery and Oncology, Tokyo Medical University,Tokyo, Japan
- Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, The State of University New York,Buffalo, NY USA
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences,Niigata, Japan
- Department of Breast Surgery, Fukushima Medical University,Fukushima, Japan
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center Elm & Carlton Streets,Buffalo, NY 14263 USA
Abstract
Purpose: Tumor-associated nerves have recently emerged as an understudied key regulator of cancer biology. However, its quantification using histological or transcriptomic approaches is challenging because their small diameters hinder reliable detection and their cell bodies that hold most mRNA reside outside the tumor. This study evaluated a Schwann cell (SC)-related transcriptomic score as a surrogate for tumor-associated nerves in tumors from triple-negative breast cancer (TNBC) patients.
Methods: Transcriptomic and clinical data from three independent TNBC cohorts, TCGA (n = 170), METABRIC (n = 335), and SCAN-B (n = 174) were analyzed. An SC score was calculated from SC-related gene signatures, and spatial transcriptomics was used to validate SC localization. In addition, seven independent neoadjuvant chemotherapy (NAC) cohorts were analyzed to evaluate the association between SC score and treatment response. Associations between the SC score and clinical features, genomic features, proliferation, treatment response, and the tumor microenvironment (TME) were evaluated.
Results: SC signature genes spatially localized to intratumoral nerve regions, confirming that the SC score reflects their presence within tumors. SC-high tumors were associated with lower mutation burden and with less cell proliferation in the TCGA, METABRIC, and SCAN-B cohorts. SC-high tumors were also associated with low immune activity and fewer infiltrating immune cells, along with enrichment of epithelial–mesenchymal transition (EMT), TGF-beta signaling and stromal remodeling pathways.
Conclusions: The SC score-high TNBC is associated with lower cell proliferation, enhanced stromal remodeling and EMT and suppressed immune activity, suggesting a role of neural-associated TME features in shaping TNBC biology.
Supplementary Information: The online version contains supplementary material available at 10.1007/
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.
The paper's code and data availability statement is in the Data section.
Tracing map
A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.
Data
Data links
- ncbi.nlm.nih.gov/
geo , NCBI; found in “Data availability”
Data availability
All data analyzed in this study are publicly available. The TCGA breast cancer datasets were obtained from cBioPortal (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 3, 28 September 2026
- Publisher: n/a → Springer Science+Business Media
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 5 keywords, 11 MeSH terms, 2 funders, 53 references.
Cite
This paper
Kawashima, K., Elsaedy, E. A., Oshi, M., Yamada, A., Narui, K., Gandhi, S., Repasky, E., Ishikawa, T., Endo, I., & Takabe, K. (2026). Association of tumor Schwann cells with epithelial-mesenchymal transition and immune-suppressive microenvironment in triple-negative breast cancer. Breast cancer research and treatment, 218(3), 37. https://
BibTeX
@article{kawashima2026as
author = {Kawashima, Kei and Elsaedy, Eslam A. and Oshi, Masanori and Yamada, Akimitsu and Narui, Kazutaka and Gandhi, Shipara and Repasky, Elizabeth and Ishikawa, Takashi and Endo, Itaru and Takabe, Kazuaki},
title = {{Association of tumor Schwann cells with epithelial-mesenchymal transition and immune-suppressive microenvironment in triple-negative breast cancer}},
journal = {Breast cancer research and treatment},
year = {2026},
month = aug,
volume = {218},
number = {3},
pages = {37},
publisher = {Springer Science+Business Media},
issn = {0167-6806},
doi = {10.1007/
url = {https://
pmid = {42573659},
pmcid = {PMC13457385}
}
RIS
TY - JOUR
AU - Kawashima, Kei
AU - Elsaedy, Eslam A.
AU - Oshi, Masanori
AU - Yamada, Akimitsu
AU - Narui, Kazutaka
AU - Gandhi, Shipara
AU - Repasky, Elizabeth
AU - Ishikawa, Takashi
AU - Endo, Itaru
AU - Takabe, Kazuaki
TI - Association of tumor Schwann cells with epithelial-mesenchymal transition and immune-suppressive microenvironment in triple-negative breast cancer
T2 - Breast cancer research and treatment
J2 - Breast Cancer Res Treat
PY - 2026
DA - 2026/
VL - 218
IS - 3
SP - 37
SN - 0167-6806
PB - Springer Science+Business Media
DO - 10.1007/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1007/
"type": "article-journal",
"title": "Association of tumor Schwann cells with epithelial-mesenchymal transition and immune-suppressive microenvironment in triple-negative breast cancer",
"container-title": "Breast cancer research and treatment",
"author": [
{
"family": "Kawashima",
"given": "Kei"
},
{
"family": "Elsaedy",
"given": "Eslam A."
},
{
"family": "Oshi",
"given": "Masanori"
},
{
"family": "Yamada",
"given": "Akimitsu"
},
{
"family": "Narui",
"given": "Kazutaka"
},
{
"family": "Gandhi",
"given": "Shipara"
},
{
"family": "Repasky",
"given": "Elizabeth"
},
{
"family": "Ishikawa",
"given": "Takashi"
},
{
"family": "Endo",
"given": "Itaru"
},
{
"family": "Takabe",
"given": "Kazuaki"
}
],
"container-title-short":
"volume": "218",
"issue": "3",
"page": "37",
"DOI": "10.1007/
"PMID": "42573659",
"PMCID": "PMC13457385",
"ISSN": "0167-6806",
"publisher": "Springer Science+Business Media",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
8,
10
]
]
}
}
Similar papers
The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.
- [1] doi:10.1016/j.xcrm.2026.102994
- Targeting of tripartite neuron-cancer-immune cell crosstalk augments response to chemotherapy and immunotherapy.Journal: Cell reports. MedicineIn common: other condition, cellular / molecular, 7 references
- [2] doi:10.1186/s13041-026-01300-7
- Hippocampal transcriptome profiling in a 22q11.2 deletion syndrome mouse model: comparison with human schizophrenia.Journal: Molecular brainIn common: genetics / omics, cellular / molecular, 2 references
- [3] doi:10.3390/ijms27156671
- Inflamed Yet Immune-Evasive? A Transcriptomic Meta-Analysis Identifies Conserved Inflammatory, Developmental, and Neuronal Signatures Associated with Polyploid Giant Cancer Cells.Journal: International journal of molecular sciencesIn common: genetics / omics, other condition, cellular / molecular, 1 reference
- [4] doi:10.1038/s41467-026-76587-0 [code]
- Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT.Journal: Nature communicationsIn common: genetics / omics, other condition, cellular / molecular, 1 reference
- [5] doi:10.1038/s12276-026-01801-4 [code]
- Putative glioblastoma origin-like cells in the subventricular zone: isolation and characterization.Journal: Experimental & molecular medicineIn common: genetics / omics, other condition, cellular / molecular, 1 reference
- [6] doi:10.1186/s12935-026-04370-8
- Machine learning-based prognostic model and single-cell transcriptomic integration for identifying brain metastasis-associated malignant subpopulations and potential therapeutic targets in lung adenocarcinoma.Journal: Cancer cell internationalIn common: genetics / omics, other condition, 1 reference
- [7] doi:10.1038/s41467-026-76683-1
- Inflammatory neuropathy in mouse and primate models of colorectal cancer.Journal: Nature communicationsIn common: other condition, cellular / molecular, 1 reference
- [8] doi:10.1038/s41392-026-02648-x
- Prostaglandin E&
lt;sub& gt;2& lt;/ sub& gt;-driven dedifferentiation of Schwann cells leads to perineural invasion in pancreatic ductal adenocarcinoma. Journal: Signal transduction and targeted therapyIn common: other condition, cellular / molecular, 1 reference - [9] doi:10.1038/s41598-026-51730-5
- Integrative bioinformatics analysis unveils neuro-cancer crosstalk-related genes and establishes prognostic risk model in Glioblastoma.Journal: Scientific reportsIn common: genetics / omics, other condition, 1 reference
- [10] doi:10.1038/s41467-026-72932-5
- Tumor-derived GDF15 induces CCN3⁺ Schwann cells to promote cancer pain in pancreatic cancer.Journal: Nature communicationsIn common: other condition, cellular / molecular, 1 reference
Contribute
The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.
Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
Request its removal
To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).
Discussion, reproductions, activity
Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.
Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.
Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.