{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:49:56Z","timestamp":1792900196906,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA234720"],"award-info":[{"award-number":["R01 CA234720"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["T32 CA080416"],"award-info":[{"award-number":["T32 CA080416"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA015704"],"award-info":[{"award-number":["P30 CA015704"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Safeway Albertson"},{"DOI":"10.13039\/100006792","name":"Hartwell Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006792","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fred Hutch&apos;s Immunotherapy Integrated Research Center"},{"name":"Bezos family"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Despite recent therapeutic progress, advanced melanoma remains lethal for many patients. The composition of the immune tumor microenvironment (TME) has decisive impacts on therapy response and disease outcome, and high-dimensional analyses of patient samples reveal the heterogeneity of the immune TME. Macrophages infiltrate TMEs and generally associate with tumor progression, but the underlying mechanisms are incompletely understood. Because experimental systems are needed to elucidate the functional properties of these cells, we developed a humanized mouse model reconstituted with human immune cells and human melanoma. We used two strains of recipient mice, supporting or not supporting the development of human myeloid cells. We found that human myeloid cells favored metastatic spread of the primary tumor, thereby recapitulating the cancer-supportive role of macrophages. We next analyzed the transcriptome of human immune cells infiltrating tumors versus other tissues. This analysis identified a cluster of myeloid cells present in the TME, but not in other tissues, which do not correspond to canonical M2 cells. The transcriptome of these cells is characterized by high expression of glycolytic enzymes and multiple chemokines and by low expression of gene sets associated with inflammation and adaptive immunity. Compared with humanized mouse results, we found transcriptionally similar myeloid cells in patient-derived samples of melanoma and other cancer types. The humanized mouse model described here thus complements patient sample analyses, enabling further elucidation of fundamental principles in melanoma biology beyond M1\/M2 macrophage polarization. The model can also support the development and evaluation of candidate antitumor therapies.<\/jats:p>","DOI":"10.4049\/jimmunol.2101109","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T04:52:42Z","timestamp":1672721562000},"page":"606-620","source":"Crossref","is-referenced-by-count":12,"title":["An In Vivo Model of Human Macrophages in Metastatic Melanoma"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5751-3881","authenticated-orcid":false,"given":"Valentin","family":"Voillet","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , Seattle, WA"},{"name":"Cape Town HIV Vaccine Trials Network Immunology Laboratory, Hutchinson Centre Research Institute of South Africa , Cape Town,","place":["South 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WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Hong","family":"Tan","sequence":"additional","affiliation":[{"name":"Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Center , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2329-8298","authenticated-orcid":false,"given":"Kimberly S","family":"Smythe","sequence":"additional","affiliation":[{"name":"Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Center , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S","family":"Hunter","sequence":"additional","affiliation":[{"name":"Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Center , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J","family":"Valente","sequence":"additional","affiliation":[{"name":"Graduate Program in Molecular and Cellular Biology, University of Washington , Seattle, WA"},{"name":"Medical Scientist Training Program, University of Washington , Seattle, WA"},{"name":"Division of Public Health Sciences, Fred Hutchinson Cancer Center , Seattle, WA"},{"name":"Human Biology Division, Fred Hutchinson Cancer Center , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Weaver","sequence":"additional","affiliation":[{"name":"Experimental Histopathology, Fred Hutchinson Cancer Center , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9187-2204","authenticated-orcid":false,"given":"Jean S","family":"Campbell","sequence":"additional","affiliation":[{"name":"Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Center , Seattle, WA"},{"name":"Department of Laboratory Medicine & Pathology, University of Washington , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6040-7748","authenticated-orcid":false,"given":"Teresa S","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Washington , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Byrd","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Washington , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason H","family":"Bielas","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences, Fred Hutchinson Cancer Center , Seattle, WA"},{"name":"Human Biology Division, Fred Hutchinson Cancer Center , Seattle, WA"},{"name":"Department of Laboratory Medicine & Pathology, University of Washington , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H","family":"Pierce","sequence":"additional","affiliation":[{"name":"Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Center , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude G","family":"Chapuis","sequence":"additional","affiliation":[{"name":"Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Center , Seattle, WA"},{"name":"Department of Medicine, University of Washington , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl","family":"Gottardo","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , Seattle, WA"},{"name":"Department of Biostatistics, University of Washington , Seattle, 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