Metabolism drives macrophage heterogeneity in the tumor microenvironment
Summary: Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment (TME). However, the relationship between the phenotype and metabolic pattern of TAMs remains poorly understood. We performed single-cell transcriptome profiling on hepatic TAMs from mice bearing...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124722003576 |
| _version_ | 1819010473331261440 |
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| author | Shasha Li Jiali Yu Amanda Huber Ilona Kryczek Zhuwen Wang Long Jiang Xiong Li Wan Du Gaopeng Li Shuang Wei Linda Vatan Wojciech Szeliga Arul M. Chinnaiyan Michael D. Green Marcin Cieslik Weiping Zou |
| author_facet | Shasha Li Jiali Yu Amanda Huber Ilona Kryczek Zhuwen Wang Long Jiang Xiong Li Wan Du Gaopeng Li Shuang Wei Linda Vatan Wojciech Szeliga Arul M. Chinnaiyan Michael D. Green Marcin Cieslik Weiping Zou |
| author_sort | Shasha Li |
| collection | DOAJ |
| description | Summary: Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment (TME). However, the relationship between the phenotype and metabolic pattern of TAMs remains poorly understood. We performed single-cell transcriptome profiling on hepatic TAMs from mice bearing liver metastatic tumors. We find that TAMs manifest high heterogeneity at the levels of transcription, development, metabolism, and function. Integrative analyses and validation experiments indicate that increased purine metabolism is a feature of TAMs with pro-tumor and terminal differentiation phenotypes. Like mouse TAMs, human TAMs are highly heterogeneous. Human TAMs with increased purine metabolism exhibit a pro-tumor phenotype and correlate with poor therapeutic efficacy to immune checkpoint blockade. Altogether, our work demonstrates that TAMs are developmentally, metabolically, and functionally heterogeneous and purine metabolism may be a key metabolic feature of a pro-tumor macrophage population. |
| first_indexed | 2024-12-21T01:12:49Z |
| format | Article |
| id | doaj.art-cf19bac1b0044715a74b077d445979ea |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T01:12:49Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-cf19bac1b0044715a74b077d445979ea2022-12-21T19:20:53ZengElsevierCell Reports2211-12472022-04-01391110609Metabolism drives macrophage heterogeneity in the tumor microenvironmentShasha Li0Jiali Yu1Amanda Huber2Ilona Kryczek3Zhuwen Wang4Long Jiang5Xiong Li6Wan Du7Gaopeng Li8Shuang Wei9Linda Vatan10Wojciech Szeliga11Arul M. Chinnaiyan12Michael D. Green13Marcin Cieslik14Weiping Zou15Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USADepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Howard Hughes Medical Institute, University of Michigan School of Medicine, Ann Arbor, MI, USACenter of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USADepartment of Computational Medicine and Bioinformatics, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Corresponding authorDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Graduate Program in Cancer Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Corresponding authorSummary: Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment (TME). However, the relationship between the phenotype and metabolic pattern of TAMs remains poorly understood. We performed single-cell transcriptome profiling on hepatic TAMs from mice bearing liver metastatic tumors. We find that TAMs manifest high heterogeneity at the levels of transcription, development, metabolism, and function. Integrative analyses and validation experiments indicate that increased purine metabolism is a feature of TAMs with pro-tumor and terminal differentiation phenotypes. Like mouse TAMs, human TAMs are highly heterogeneous. Human TAMs with increased purine metabolism exhibit a pro-tumor phenotype and correlate with poor therapeutic efficacy to immune checkpoint blockade. Altogether, our work demonstrates that TAMs are developmentally, metabolically, and functionally heterogeneous and purine metabolism may be a key metabolic feature of a pro-tumor macrophage population.http://www.sciencedirect.com/science/article/pii/S2211124722003576CP: CancerCP: Metabolism |
| spellingShingle | Shasha Li Jiali Yu Amanda Huber Ilona Kryczek Zhuwen Wang Long Jiang Xiong Li Wan Du Gaopeng Li Shuang Wei Linda Vatan Wojciech Szeliga Arul M. Chinnaiyan Michael D. Green Marcin Cieslik Weiping Zou Metabolism drives macrophage heterogeneity in the tumor microenvironment Cell Reports CP: Cancer CP: Metabolism |
| title | Metabolism drives macrophage heterogeneity in the tumor microenvironment |
| title_full | Metabolism drives macrophage heterogeneity in the tumor microenvironment |
| title_fullStr | Metabolism drives macrophage heterogeneity in the tumor microenvironment |
| title_full_unstemmed | Metabolism drives macrophage heterogeneity in the tumor microenvironment |
| title_short | Metabolism drives macrophage heterogeneity in the tumor microenvironment |
| title_sort | metabolism drives macrophage heterogeneity in the tumor microenvironment |
| topic | CP: Cancer CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124722003576 |
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