CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation
Open accessAbstract
Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. Upregulation of CD45 tyrosine phosphatase activity in MDSCs exposed to hypoxia in tumor site was responsible for downregulation of STAT3. This effect was mediated by the disruption of CD45 protein dimerization regulated by sialic acid. Thus, STAT3 has a unique function in the tumor environment in controlling the differentiation of MDSC into TAM, and its regulatory pathway could be a potential target for therapy.
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HIFs can switch tumor-associated macrophages from an antitumorigenic M1-like phenotype to a protumorigenic M2-like phenotype.
“HIFs can also switch tumor‐associated macrophages (TAMs) from an antitumorigenic (M1‐like) phenotype to a protumorigenic (M2‐like) phenotype.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [119]
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References 42 · Cited by 371
- Authors
- Kumar, V., Cheng, P., Condamine, T., Mony, S., Languino, L. R., McCaffrey, J. C., Hockstein, N., Guarino, M., Masters, G., Penman, E., Denstman, F., Xu, X., Altieri, D. C., Du, H., Yan, C., & Gabrilovich, D. I.
- Affiliations
- The Wistar Institute (US)
- Moffitt Cancer Center (US)
- Thomas Jefferson University (US)
- Christiana Care Health System (US)
- University of Pennsylvania (US)
- Indiana University School of Medicine (US)
- Corresponding author
- Gabrilovich, Dmitry I.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 44
- Issue
- 2
- Pages
- 303-315
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4759655
- OpenAlex
- W2275956983
- Cited by
- 371
- References
- 42
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 36 · 2023: 36 · 2022: 53 · 2021: 44 · 2020: 44 · 2019: 34 · 2018: 33 · 2017: 33 · 2016: 18 · 2014: 1
- FWCI
- 23.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- Funders
- National Cancer Institute (R01CA078810, CA100062, R01CA152099, R01CA190027, CA177646, P01CA114046, R01CA177646, R01CA138759, P01CA140043, R01CA100062, P50CA174523, P30CA010815)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- STAT3, tumor-associated macrophages, myeloid-derived suppressor cells, hypoxia, sialic acid, macrophage differentiation, tumor microenvironment, myeloid cells, transcription factor regulation
- MeSH terms
- Animals, Hypoxia, Cell Differentiation, Cell Movement, Cells, Cultured, Female, Macrophages, Mice, Inbred BALB C, Mice, Inbred C57BL, Phosphoric Monoester Hydrolases, Sialic Acids, Leukocyte Common Antigens, Mice, Knockout, Dimerization, Myeloid Cells, STAT3 Transcription Factor, Mice, Tumor Microenvironment
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