Comparison of NSG-Quad and MISTRG-6 humanized mice for modeling circulating and tumor-infiltrating human myeloid cells
Humanized mice are valuable preclinical models for immuno-oncology research because they allow modeling of human immune cells and human tumors in vivo. Myeloid cells are highly abundant in many tumors and have been associated with tumor progression, metastasis, and therapy resistance. Next-generatio...
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Elsevier
2025-06-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050125000828 |
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| author | Anna Chen Viktoria Knöbl Oliver Walzer Jana Hauser Ines Neuwirth Magdalena Frank Nina Braun Semina Duvnjak Johannes Reisecker Carmen Stecher Alex Farr Christine Brostjan Dietmar Herndler-Brandstetter |
| author_facet | Anna Chen Viktoria Knöbl Oliver Walzer Jana Hauser Ines Neuwirth Magdalena Frank Nina Braun Semina Duvnjak Johannes Reisecker Carmen Stecher Alex Farr Christine Brostjan Dietmar Herndler-Brandstetter |
| author_sort | Anna Chen |
| collection | DOAJ |
| description | Humanized mice are valuable preclinical models for immuno-oncology research because they allow modeling of human immune cells and human tumors in vivo. Myeloid cells are highly abundant in many tumors and have been associated with tumor progression, metastasis, and therapy resistance. Next-generation humanized mice have been generated to improve the development, diversity, and function of human myeloid cells. In this study, we analyzed human immune cell development and myeloid cell composition in NSG-Quad and MISTRG-6 mice. NSG-Quad mice supported the development of tissue-resident and tumor-infiltrating human macrophages at levels almost comparable to those of MISTRG-6 mice. However, the development of human CD4+ and CD8+ T cells was impaired in the blood and spleen but not in the tumor of NSG-Quad mice. In a subset of NSG-Quad mice, human monocytes exhibited increased cellular granularity and elevated expression of activation and checkpoint molecules, consistent with a monocyte hyperactivation syndrome. Our study provides a comprehensive comparative analysis of the frequency and characteristics of circulating, tissue-resident, and tumor-infiltrating myeloid cell populations in NSG-Quad and MISTRG-6 mice, which is key to accurately design and interpret human tumor xenograft studies, particularly with regard to faithful reconstruction of the human tumor-immune microenvironment and preclinical testing. |
| format | Article |
| id | doaj-art-2693cc092e8b45e49c755b142e39015b |
| institution | OA Journals |
| issn | 2329-0501 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj-art-2693cc092e8b45e49c755b142e39015b2025-08-20T01:57:08ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012025-06-0133210148710.1016/j.omtm.2025.101487Comparison of NSG-Quad and MISTRG-6 humanized mice for modeling circulating and tumor-infiltrating human myeloid cellsAnna Chen0Viktoria Knöbl1Oliver Walzer2Jana Hauser3Ines Neuwirth4Magdalena Frank5Nina Braun6Semina Duvnjak7Johannes Reisecker8Carmen Stecher9Alex Farr10Christine Brostjan11Dietmar Herndler-Brandstetter12Center for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, AustriaDepartment of General Surgery, Division of Vascular Surgery, Medical University of Vienna, 1090 Vienna, AustriaCenter for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, AustriaCenter for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, AustriaCenter for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, AustriaCenter for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, AustriaCenter for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, AustriaCenter for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, AustriaCenter for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, AustriaCenter for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, AustriaDepartment of Obstetrics and Gynecology, Division of Obstetrics and Feto-Maternal Medicine, Medical University of Vienna and Comprehensive Center for Pediatrics (CCP), Medical University of Vienna, 1090 Vienna, AustriaDepartment of General Surgery, Division of Vascular Surgery, Medical University of Vienna, 1090 Vienna, AustriaCenter for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, Austria; Corresponding author: Dietmar Herndler-Brandstetter, Center for Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090 Vienna, Austria.Humanized mice are valuable preclinical models for immuno-oncology research because they allow modeling of human immune cells and human tumors in vivo. Myeloid cells are highly abundant in many tumors and have been associated with tumor progression, metastasis, and therapy resistance. Next-generation humanized mice have been generated to improve the development, diversity, and function of human myeloid cells. In this study, we analyzed human immune cell development and myeloid cell composition in NSG-Quad and MISTRG-6 mice. NSG-Quad mice supported the development of tissue-resident and tumor-infiltrating human macrophages at levels almost comparable to those of MISTRG-6 mice. However, the development of human CD4+ and CD8+ T cells was impaired in the blood and spleen but not in the tumor of NSG-Quad mice. In a subset of NSG-Quad mice, human monocytes exhibited increased cellular granularity and elevated expression of activation and checkpoint molecules, consistent with a monocyte hyperactivation syndrome. Our study provides a comprehensive comparative analysis of the frequency and characteristics of circulating, tissue-resident, and tumor-infiltrating myeloid cell populations in NSG-Quad and MISTRG-6 mice, which is key to accurately design and interpret human tumor xenograft studies, particularly with regard to faithful reconstruction of the human tumor-immune microenvironment and preclinical testing.http://www.sciencedirect.com/science/article/pii/S2329050125000828colorectal cancerNSG-QuadMISTRG-6human immune system miceimmuno-oncologytumor microenvironment |
| spellingShingle | Anna Chen Viktoria Knöbl Oliver Walzer Jana Hauser Ines Neuwirth Magdalena Frank Nina Braun Semina Duvnjak Johannes Reisecker Carmen Stecher Alex Farr Christine Brostjan Dietmar Herndler-Brandstetter Comparison of NSG-Quad and MISTRG-6 humanized mice for modeling circulating and tumor-infiltrating human myeloid cells Molecular Therapy: Methods & Clinical Development colorectal cancer NSG-Quad MISTRG-6 human immune system mice immuno-oncology tumor microenvironment |
| title | Comparison of NSG-Quad and MISTRG-6 humanized mice for modeling circulating and tumor-infiltrating human myeloid cells |
| title_full | Comparison of NSG-Quad and MISTRG-6 humanized mice for modeling circulating and tumor-infiltrating human myeloid cells |
| title_fullStr | Comparison of NSG-Quad and MISTRG-6 humanized mice for modeling circulating and tumor-infiltrating human myeloid cells |
| title_full_unstemmed | Comparison of NSG-Quad and MISTRG-6 humanized mice for modeling circulating and tumor-infiltrating human myeloid cells |
| title_short | Comparison of NSG-Quad and MISTRG-6 humanized mice for modeling circulating and tumor-infiltrating human myeloid cells |
| title_sort | comparison of nsg quad and mistrg 6 humanized mice for modeling circulating and tumor infiltrating human myeloid cells |
| topic | colorectal cancer NSG-Quad MISTRG-6 human immune system mice immuno-oncology tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2329050125000828 |
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