Interleukin-34-Induced Arg1+ Macrophages Play a Key Role in Breast Cancer Brain Metastasis.
Overview
and 8 other authors
Nathan M Merrill5, Sofia Diana Merajver5, Qingyun Li11,12,13, Katherine Schwetye9,10, Vaibhav Jain2, Simon G Gregory2,14,15, Albert H Kim3,11,12,16, Ron Bose1,916 affiliations
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina
- Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
- Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan
- Duke Center for Brain and Spine Metastasis, Duke University School of Medicine, Durham, North Carolina
- Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri
- Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri
- Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri
- Department of Genetics, Washington University School of Medicine, St. Louis, Missouri
- The Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine, Durham, North Carolina
- Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina
- The Brain Tumor Center, Washington University School of Medicine, St. Louis, Missouri
Abstract
Brain metastases occur in up to 40% of patients with stage IV breast cancer, and the cerebellum is a common site for metastases in HER2-positive breast cancer. We developed a syngeneic, immunocompetent mouse model of breast cancer brain metastases (BCBM) by stereotactically injecting murine breast cancer organoids into the cerebellum. Spatial transcriptomics on these brain metastases revealed that breast cancer cells produce interleukin-34 (IL34), which induces ARG1+ macrophages at the invading edge of metastases. IL34 expression in human brain metastasis samples was measured in two independent datasets, and IL34 was expressed widely in both HER2+ and HER2− human BCBM. Remarkably, IL34-deficient breast cancer cells failed to establish tumors in the mouse cerebellum. Furthermore, treatment with a blocking antibody against the IL34 receptor, CSF1R, led to tumor shrinkage, highlighting the translational potential of these findings, as a CSF1R-blocking antibody is FDA-approved for another indication, graft-versus-host disease.
Significance: Targeting IL34–CSF1R is a potential new approach to treat BCBM and could be combined with existing therapies. IL34 expression is widely found in human BCBM.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- geo:GSE325996, at NCBI GEO; found in “Data Availability”
Data Availability
Spatial transcriptomics data generated in this study are deposited in the Gene Expression Omnibus, accession code GSE325996 (https://
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Reproduced under the paper's license (CC BY), from the paper cited above.
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Recorded: type, language, journal, volume, issue, pages, dates, 28 authors, 10 MeSH terms, 5 funders, 66 references, 21 RRIDs.
Cite
This paper
Cheng, X., Patel, K. K., Zhou, B., Fu, Y., Cleary, R. T., Highkin, M., Hsia, J., Jin, X., Kohn, B., Prior, J. L., Michie, M. S., Sun, R., Cheng, X., Bao, L., Heth, J., Rastogi, T., Van Swearingen, A. E., Quirk, J. D., Hagemann, I. S., . . . Bose, R. (2026). Interleukin-34-Induced Arg1+ Macrophages Play a Key Role in Breast Cancer Brain Metastasis. Cancer research communications, 6(6), 1388-1404. https://
BibTeX
@article{cheng2026interl
author = {Cheng, Xiaoqing and Patel, Khooshbu K and Zhou, Brandon and Fu, Yiwei and Cleary, Ryan T and Highkin, Maureen and Hsia, Jacob and Jin, Xiaohua and Kohn, Benjamin and Prior, Julie L and Michie, Megan S and Sun, Rui and Cheng, Xu and Bao, Liwei and Heth, Jason and Rastogi, Tusharika and Van Swearingen, Amanda ED and Quirk, James D and Hagemann, Ian S and Morikawa, Aki and Merrill, Nathan M and Merajver, Sofia Diana and Li, Qingyun and Schwetye, Katherine and Jain, Vaibhav and Gregory, Simon G and Kim, Albert H and Bose, Ron},
title = {{Interleukin-34-Induced
journal = {Cancer research communications},
year = {2026},
month = jun,
volume = {6},
number = {6},
pages = {1388--1404},
publisher = {American Association for Cancer Research},
issn = {2767-9764},
doi = {10.1158/
url = {https://
pmid = {42166785},
pmcid = {PMC13261624}
}
RIS
TY - JOUR
AU - Cheng, Xiaoqing
AU - Patel, Khooshbu K
AU - Zhou, Brandon
AU - Fu, Yiwei
AU - Cleary, Ryan T
AU - Highkin, Maureen
AU - Hsia, Jacob
AU - Jin, Xiaohua
AU - Kohn, Benjamin
AU - Prior, Julie L
AU - Michie, Megan S
AU - Sun, Rui
AU - Cheng, Xu
AU - Bao, Liwei
AU - Heth, Jason
AU - Rastogi, Tusharika
AU - Van Swearingen, Amanda ED
AU - Quirk, James D
AU - Hagemann, Ian S
AU - Morikawa, Aki
AU - Merrill, Nathan M
AU - Merajver, Sofia Diana
AU - Li, Qingyun
AU - Schwetye, Katherine
AU - Jain, Vaibhav
AU - Gregory, Simon G
AU - Kim, Albert H
AU - Bose, Ron
TI - Interleukin-34-Induced Arg1+ Macrophages Play a Key Role in Breast Cancer Brain Metastasis
T2 - Cancer research communications
J2 - Cancer Res Commun
PY - 2026
DA - 2026/
VL - 6
IS - 6
SP - 1388
EP - 1404
SN - 2767-9764
PB - American Association for Cancer Research
DO - 10.1158/
UR - https://
LA - en
ER -
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