ArticleCell2026
Unbiased niche labeling maps immune-excluded niche in bone metastasis.
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In one paragraph
Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4citing papers in PubMed
–field-weighted citation impact
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Who cites it
4 citing papers in PubMed.
- ICAM1high Neutrophils Sculpt Tumor Evolution and Metastasis Through Symbiotic Adhesion and Reverse Migration.Cancer research · 2026Article
- Breaking the immune "cold niche" in bone metastasis: core mechanisms of the multidimensional interwoven regulatory network and precision breakthrough strategies.Molecular cancer · 2026Review
- From Bone Marrow Reserve to Metastatic Niche: How Neutrophil-Lineage Cells Shape Skeletal Colonization.International journal of molecular sciences · 2026Review
- Vascular-immune zonation sets organ-specific metastatic checkpoints.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
30 authors.
Zhan XuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Fengshuo LiuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Yunfeng DingLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Tianhong PanDepartment of Orthopedic Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Yi-Hsuan WuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Yujiao HanDepartment of Molecular Biology, Princeton University, Princeton, Princeton, NJ 08544, USA; Ludwig Institute for Cancer Research Princeton Branch, Princeton, Princeton, NJ 08544, USA.
Jun LiuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Igor L BadoIcahn School of Medicine, Mount Sinai, New York, NY 10029, USA; Mount Sinai Tisch Cancer Center, New York, NY 10029, USA; Department of Oncological Sciences, Mount Sinai, New York, NY 10029, USA.
Weijie ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Ling WuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Yang GaoDepartment of Cancer Biology and Genetics, The Ohio State University College of Medicine, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Xiaoxin HaoLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Liqun YuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Xuan LiLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
David G EdwardsLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Hilda L ChanLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; The Robert and Janice McNair Foundation MD/PhD Scholars, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA.
Sergio AguirreLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Michael Warren DieffenbachLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Development, Disease Models, and Therapeutics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Elina ChenCollege of Natural Sciences, University of Texas at Austin, 110 Inner Campus Drive, Austin, TX 78706, USA.
Siyue WangLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Yichao ShenLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Dane HoffmanLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Luis Becerra DominguezLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Charlotte Helena RivasLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Xiang ChenLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Hai WangDepartment of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Yibin KangDepartment of Molecular Biology, Princeton University, Princeton, Princeton, NJ 08544, USA; Ludwig Institute for Cancer Research Princeton Branch, Princeton, Princeton, NJ 08544, USA; Cancer Metabolism and Immunology Program, Rutgers Cancer Institute, New Brunswick, NJ 08903, USA.
Zbigniew GugalaDepartment of Orthopedic Surgery and Rehabilitation, University of Texas Medical Branch, Galveston, TX 77555, USA.
Robert L SatcherDepartment of Orthopedic Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Xiang H-F ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: xiangz@bcm.edu.
Funding
Translational Research in Breast Cancer (SPORE)P50CA186784 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Xiang Zhang · 2014 to 2026
$24.5MOsteoclast-Independent Mechanisms of Early-Stage Bone Colonization of Breast CancerR01CA183878 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, XIANG · 2014 to 2024
$3.5MNext Generation Rat Models of ER+ Breast CancerR01CA271498 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Yi Li, Xiang Zhang · 2022 to 2026
$3.1MSpatiotemporal modeling of cancer-niche interactions in breast cancer bone metastasisU01CA253553 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI WONG, STEPHEN TC, ZHANG, XIANG · 2020 to 2024
$3.0MUnveiling the mechanisms underlying secondary metastasis and possible therapeutic windowsR01CA251950 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, XIANG · 2020 to 2024
$2.6MModulation of Epigenetic Target in the Bone to Treat Breast Cancer MetastasisR01CA277838 · NCI · RICE UNIVERSITY · PI Han Xiao, Xiang Zhang · 2023 to 2026
$2.6MHarnessing neutrophils to improve the efficacy of immune checkpoint inhibitors in breast cancerR00CA279899 · NCI · OHIO STATE UNIVERSITY · PI Yang Gao · 2025 to 2026
$497kHarnessing neutrophils to improve the efficacy of immune checkpoint inhibitors in breast cancerK99CA279899 · NCI · BAYLOR COLLEGE OF MEDICINE · PI GAO, YANG · 2023 to 2024
$238kNCI NIH HHS K99 CA279899NCI NIH HHS P50 CA186784NCI NIH HHS R00 CA279899NCI NIH HHS R01 CA183878NCI NIH HHS R01 CA251950NCI NIH HHS R01 CA271498NCI NIH HHS R01 CA277838NCI NIH HHS U01 CA253553
Abstract
Metastatic cancer cell fate is shaped by the local microenvironment niches. To unbiasedly define the cellular and molecular features of metastatic niches, we developed sortase A-based microenvironment niche tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastasis. Applying SAMENT across multiple cancer models and target organs revealed shared niche features, including macrophage enrichment and T cell depletion, alongside marked organ-specific phenotype heterogeneity in niche macrophages. In bone, metastatic niches are enriched for macrophages expressing estrogen receptor alpha (ERα) with active ERα signaling. Conditional deletion of Esr1 in macrophages significantly impaired bone colonization by enabling T cell infiltration. ERα⁺ macrophages were also identified in human bone metastases across multiple cancer types. Together, these findings define a distinct ERα⁺ macrophage niche and establish macrophage ERα signaling as a key driver of T cell exclusion during metastatic colonization.
Indexed as
Bone NeoplasmsTumor MicroenvironmentAminoacyltransferasesAnimalsBacterial ProteinsCysteine EndopeptidasesEstrogen Receptor alphaFemaleHumansMacrophagesMiceNeoplasm MetastasisSignal TransductionT-LymphocytesAminoacyltransferasesBacterial ProteinsCysteine EndopeptidasesEstrogen Receptor alphasortase Abone metastasisestrogen receptorestrogen signalingfatty acidimmune exclusionmacrophagemetastatic nicheniche labelingsortase Atumor microenvironment
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