{"doi":"10.1101/2025.06.17.660224","title":"Cerebellum metastasis model of HER2-positive breast cancer unveils key role of IL34-induced Arg1+ macrophages","abstract":"Brain metastases occur in up to 40% of Stage IV breast cancer patients. The cerebellum is a frequent location for metastases in HER2-positive breast cancer patients, but the mechanisms for this are unknown. Here, we developed a syngeneic, immunocompetent mouse model for breast cancer brain metastases by stereotactically injecting mouse HER2-overexpressing breast cancer organoids into the cerebellum. Growth of these cerebellar metastases was monitored by MRI and trastuzumab optical imaging using a near-infrared fluorophore conjugated to trastuzumab. Spatial transcriptomics identified interleukin-34 production by breast cancer cells inducing ARG1+ macrophages at the invading edge of the metastasis. Treatment with a blocking antibody to interleukin-34's receptor, CSF1R, produced tumor shrinkage. These findings have immediate translation potential as a CSF1R-blocking antibody is FDA-approved. Further, it demonstrates that cancer-associated inflammation bordering the brain metastasis promotes metastatic growth and offers a molecularly targeted strategy to treat inflammation in brain metastasis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558308,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1397899,"name":"Khooshbu Kantibhai Patel","orcid":"0000-0002-7575-4734","position":1,"is_corresponding":false},{"id":1010859,"name":"Brandon Zhou","orcid":"0000-0002-7054-4033","position":2,"is_corresponding":false},{"id":1458733,"name":"Yiwei Fu","orcid":"0000-0002-2450-3804","position":3,"is_corresponding":false},{"id":743980,"name":"Ryan Cleary","orcid":null,"position":4,"is_corresponding":false},{"id":266769,"name":"Maureen Highkin","orcid":"0009-0005-5923-7883","position":5,"is_corresponding":false},{"id":1459181,"name":"Jacob Hsia","orcid":null,"position":6,"is_corresponding":false},{"id":1458734,"name":"Xiaohua Jin","orcid":"0000-0001-9249-7496","position":7,"is_corresponding":false},{"id":1459182,"name":"Beth Kohn","orcid":null,"position":8,"is_corresponding":false},{"id":425903,"name":"Julie L. Prior","orcid":"0009-0009-0292-1552","position":9,"is_corresponding":false},{"id":289137,"name":"Megan S. Michie","orcid":"0000-0001-8749-4063","position":10,"is_corresponding":false},{"id":445255,"name":"Rui Sun","orcid":"0000-0003-4054-1365","position":11,"is_corresponding":false},{"id":267505,"name":"Amanda E.D. Van Swearingen","orcid":"0000-0002-4287-9741","position":12,"is_corresponding":false},{"id":274285,"name":"James D. Quirk","orcid":"0000-0002-6118-7097","position":13,"is_corresponding":false},{"id":231283,"name":"Ian S. Hagemann","orcid":"0000-0002-3855-9745","position":14,"is_corresponding":false},{"id":1459183,"name":"Tristan Li","orcid":null,"position":15,"is_corresponding":false},{"id":992026,"name":"Vaibhav Jain","orcid":"0000-0003-0374-8383","position":16,"is_corresponding":false},{"id":59323,"name":"Simon G. Gregory","orcid":"0000-0002-7805-1743","position":17,"is_corresponding":false},{"id":1091419,"name":"Albert Kim","orcid":"0000-0003-1539-1246","position":18,"is_corresponding":false},{"id":278297,"name":"Ron Bose","orcid":"0000-0003-1977-8894","position":19,"is_corresponding":false},{"id":772333,"name":"Xiaoqing Cheng","orcid":"0000-0001-5321-1459","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:55:25.969263Z","pmid":"40666928","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}