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However, approximately 50% of patients do not respond to ICI, and the brain-specific interactions that shape anti-tumor immunity remain poorly understood. We profiled five syngeneic BM models using spatial transcriptomics, identifying myeloid-rich niches enriched for interferon-responsive and disease-associated microglia (DAM)-like programs. Ligand-receptor colocalization analyses identified progranulin (PGRN) as a candidate mediator of these niches. Host- or tumor-cell\n                  <jats:italic>Grn<\/jats:italic>\n                  loss reduced BM burden, and\n                  <jats:italic>Grn<\/jats:italic>\n                  -deficient macrophages exhibited altered metabolic programs and tumor-cell engulfment in vitro. Across independent human BM datasets,\n                  <jats:italic>GRN<\/jats:italic>\n                  expression was associated with conserved lysosomal and DAM-like myeloid programs, and\n                  <jats:italic>GRN<\/jats:italic>\n                  -high myeloid regions colocalized with immunosuppressive signatures and dysfunctional CD8+ T cell states. These cross-species findings identify PGRN as a candidate mediator of the BM immune niche and support further investigation of its therapeutic relevance.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>A multi-model spatial atlas resolves myeloid niches in both preclinical models of brain metastases and human patient tissues<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Host- and tumor-cell progranulin support brain metastatic growth<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Progranulin associates with lysosomal function and disease-associated myeloid states in brain metastasis<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Human progranulin-rich myeloid niches colocalize with dysfunctional cytotoxic T cells in brain metastasis<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"751277v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.13.751277","type":"posted-content","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:35:11Z","timestamp":1789875311000},"source":"Crossref","is-referenced-by-count":0,"title":["Cross-species spatial profiling links progranulin to an immune suppressive niche in brain metastasis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-4769","authenticated-orcid":false,"given":"Nicole M.","family":"Eskow","sequence":"first","affiliation":[{"name":"Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, United States"},{"name":"Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, NY, 10016, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2845-2458","authenticated-orcid":false,"given":"Kylie","family":"Prutisto-Chang","sequence":"additional","affiliation":[{"name":"Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, United States"},{"name":"Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, NY, 10016, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6478-8197","authenticated-orcid":false,"given":"Maria A.","family":"Gomez-Munoz","sequence":"additional","affiliation":[{"name":"Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, United States"},{"name":"Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, NY, 10016, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irineu Illa","family":"Bochaca","sequence":"additional","affiliation":[{"name":"Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, United States"},{"name":"Interdisciplinary Melanoma Cooperative Group, 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