Deletion of TGF-β signaling in myeloid cells enhances their anti-tumorigenic properties
Open accessAbstract
Specific deletion of TGF-β receptor II in macrophages, CD11b+Gr1+, and dendritic cells inhibit tumor growth by increasing efficiency of the immune system. By crossing LysM-Cre and TGF-β type II receptor (Tgfbr2) floxed mice we achieved specific deletion of Tgfbr2 in myeloid cells (Tgfbr2MyeKO mice). S.c.-injected (LLC, EL4-OVA) and implanted (MMTV-PyMT) carcinoma cells grow slower in Tgfbr2MyeKO mice. The number of CD45+ cells in the tumor tissue was the same in both genotypes of mice, but upon analysis, the percentage of T cells (CD45+CD3+) in the KO mice was increased. By flow cytometry analysis, we did not detect any differences in the number and phenotype of TAMs, CD11b+Gr1+, and DCs in Tgfbr2MyeKO compared with Tgfbr2MyeWT mice. ELISA and qRT-PCR data showed differences in myeloid cell functions. In Tgfbr2MyeKO TAMs, TNF-α secretion was increased, basal IL-6 secretion was down-regulated, TGF-β did not induce any VEGF response, and there was decreased MMP9 and increased MMP2 and iNOS expression. TGF-β did not have any effect on CD11b+Gr1+ cells isolated from Tgfbr2MyeKO mice in the regulation of Arg, iNOS, VEGF, and CXCR4, and moreover, these cells have decreased suppressive activity relative to T cell proliferation. Also, we found that DCs from tumor tissue of Tgfbr2MyeKO mice have increased antigen-presented properties and an enhanced ability to stimulate antigen-specific T cell proliferation. We conclude that Tgfbr2 in myeloid cells has a negative role in the regulation of anti-tumorigenic functions of these cells, and deletion of this receptor decreases the suppressive function of CD11b+Gr1+ cells and increases antigen-presenting properties of DCs and anti-tumorigenic properties of TAMs.
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TGF-β suppresses the expression of IL-2 and its receptor by effector and memory T cells.
“TGF-β suppresses the expression of IL-2 and its receptor by effector and memory T cells205.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [205]
CD8+ T cell proliferation requires IL-2 expression and responsiveness.
“CD8+ T cell proliferation additionally requires interleukin (IL)-2 expression and responsiveness”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [205]
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- Authors
- Novitskiy, S. V., Pickup, M. W., Chytil, A., Polosukhina, D., Owens, P., & Moses, H. L.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Moses, Harold L
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-06-08
- Volume
- 92
- Issue
- 3
- Pages
- 641-651
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- PMC
- PMC3427612
- OpenAlex
- W2168336731
- Cited by
- 79
- References
- 52
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 9 · 2019: 5 · 2018: 9 · 2017: 7 · 2016: 2 · 2015: 6 · 2014: 5 · 2013: 5 · 2012: 1
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. National Institutes of Health (CA085492, A102162, CA126505)
- T.J. Martell Foundation (CA068485)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- TGF-beta signaling, TGFBR2, myeloid cells, tumor-associated macrophages, tumor-infiltrating lymphocytes, dendritic cells, tumor immunosuppression, TNF-α, interleukin-6, vascular endothelial growth factor, MMP-9, inducible nitric oxide synthase, CXCR4, antigen presentation, T cell proliferation
- MeSH terms
- Receptor, Transforming Growth Factor-beta Type II, Animals, Cell Separation, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Macrophages, Neoplasms, Experimental, Signal Transduction, Transforming Growth Factor beta, Protein Serine-Threonine Kinases, Antigen Presentation, Receptors, Transforming Growth Factor beta, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Myeloid Cells, Mice, Tumor Microenvironment
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