Interleukin-34 induced Arg1+ macrophages play a key role in breast cancer brain metastasis.
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 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 breast cancer brain metastasis. Remarkably, IL34-deficient breast cancer cells failed to establish tumors in the mouse cerebellum. Further, 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.
Authors
- Ron Bose (ORCID: https://orcid.org/0000-0003-1977-8894)
- Amanda E.D. Van Swearingen (ORCID: https://orcid.org/0000-0002-4287-9741)
- Xiaohua Jin (ORCID: https://orcid.org/0000-0001-9249-7496)
- Ryan T. Cleary (ORCID: https://orcid.org/0000-0002-2018-3559)
- Beth Kohn
- Brandon Zhou (ORCID: https://orcid.org/0000-0002-7054-4033)
- Nathan Merrill (ORCID: https://orcid.org/0000-0003-0757-3680)
- Megan S. Michie (ORCID: https://orcid.org/0000-0001-8749-4063)
- Yiwei Fu (ORCID: https://orcid.org/0000-0002-2450-3804)
- Julie L. Prior (ORCID: https://orcid.org/0009-0009-0292-1552)
- Jacob Hsia (ORCID: https://orcid.org/0009-0004-4847-195X)
- Rui Sun (ORCID: https://orcid.org/0000-0003-4054-1365)
- Tusharika Rastogi
- Simon G. Gregory
- Jason Heth
- Ian S. Hagemann (ORCID: https://orcid.org/0000-0002-3855-9745)
- Albert H. Kim (ORCID: https://orcid.org/0000-0002-1751-8493)
- Xu Cheng (ORCID: https://orcid.org/0009-0009-8385-3108)
- James D. Quirk (ORCID: https://orcid.org/0000-0002-6118-7097)
- Sofia Diana. Merajver (ORCID: https://orcid.org/0000-0002-6823-7130)
- Maureen Highkin (ORCID: https://orcid.org/0009-0005-5923-7883)
- Liwei Bao (ORCID: https://orcid.org/0009-0008-0095-1443)
- Aki Morikawa (ORCID: https://orcid.org/0000-0002-4764-4896)
- Qingyun Li (ORCID: https://orcid.org/0000-0002-3457-5967)
- Vaibhav Jain (ORCID: https://orcid.org/0000-0002-9235-6236)
- Khooshbu K. Patel (ORCID: https://orcid.org/0000-0002-7575-4734)
- Katherine Schwetye (ORCID: https://orcid.org/0000-0002-0885-2764)
- Xiaoqing Cheng (ORCID: https://orcid.org/0000-0001-5321-1459)
Institutions
- Duke University (US)
- Virginia Commonwealth University (US)
- Washington University in St. Louis (US)
- University of Michigan (US)
- Clinical Research Institute (US)
- Michigan Medicine (US)
- Duke Institute for Health Innovation (US)
- Duke Medical Center (US)
- Ann Arbor Center for Independent Living (US)
- Duke University Hospital (US)
Publication Details
- Journal
- Cancer Research Communications
- Published
- 2026-05-21
- DOI
- https://doi.org/10.1158/2767-9764.crc-25-0639
- Primary Topic
- Brain Metastases and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00