The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Subpopulations of myeloid‐derived suppressor cells impair T cell responses through independent nitric oxide‐related pathways
Open accessAbstract
The accumulation of myeloid‐derived suppressor cells (MDSC) in tumor‐bearing hosts is a hallmark of malignancy‐associated inflammation and a major mediator for the induction of T cell suppression in cancer. MDSC can be divided phenotypically into granulocytic (G‐MDSC) and monocytic (Mo‐MDSC) subgroups. Several mechanisms mediate the induction of T cell anergy by MDSC; however, the specific role of these pathways in the inhibitory activity of MDSC subpopulations remains unclear. Therefore, we aimed to determine the effector mechanisms by which subsets of tumor‐infiltrating MDSC block T cell function. We found that G‐MDSC had a higher ability to impair proliferation and expression of effector molecules in activated T cells, as compared to Mo‐MDSC. Interestingly, both MDSC subgroups inhibited T cells through nitric oxide (NO)‐related pathways, but expressed different effector inhibitory mechanisms. Specifically, G‐MDSC impaired T cells through the production of peroxynitrites (PNT), while Mo‐MDSC suppressed by the release of NO. The production of PNT in G‐MDSC depended on the expression of gp91 phox and endothelial NO synthase (eNOS), while inducible NO synthase (iNOS) mediated the generation of NO in Mo‐MDSC. Deletion of eNOS and gp91 phox or scavenging of PNT blocked the suppressive function of G‐MDSC and induced anti‐tumoral effects, without altering Mo‐MDSC inhibitory activity. Furthermore, NO‐scavenging or iNOS knockdown prevented Mo‐MDSC function, but did not affect PNT production or suppression by G‐MDSC. These results suggest that MDSC subpopulations utilize independent effector mechanisms to regulate T cell function. Inhibition of these pathways is expected to specifically block MDSC subsets and overcome immune suppression in cancer.
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Cites
Myeloid-derived-suppressor cells as regulators of the immune system
Gabrilovich, D. I., & Nagaraj, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2506 · Cited by 6,753
Coordinated regulation of myeloid cells by tumours
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Subsets of Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice
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Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer
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Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet?
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Myeloid-Derived Suppressor Cells Inhibit T-Cell Activation by Depleting Cystine and Cysteine
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Self-citationZea, A. H., Rodriguez, P. C., Atkins, M. B., Hernandez, C., Signoretti, S., Zabaleta, J., McDermott, D., Quiceno, D., Youmans, A., O'Neill, A., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4505 · Cited by 851
Self-citationKusmartsev, S., Nefedova, Y., Yoder, D., & Gabrilovich, D. I. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.2.989 · Cited by 850
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Approaches to treat immune hot, altered and cold tumours with combination immunotherapies
Galon, J., & Bruni, D. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0007-y · Cited by 3,409
Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards
Bronte, V., Brandau, S., Chen, S.-H., Colombo, M. P., Frey, A. B., Greten, T. F., Mandruzzato, S., Murray, P. J., Ochoa, A., Ostrand-Rosenberg, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms12150 · Cited by 2,751
Self-citationThe Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment
Kumar, V., Patel, S., Tcyganov, E., & Gabrilovich, D. I. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.01.004 · Cited by 2,008
Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity
Veglia, F., Sanseviero, E., & Gabrilovich, D. I. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00490-y · Cited by 1,940
Myeloid-Derived Suppressor Cells
Gabrilovich, D. I. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0297 · Cited by 1,882
Metadata
- Authors
- Raber, P. L., Thevenot, P., Sierra, R., Wyczechowska, D., Halle, D., Ramirez, M. E., Ochoa, A. C., Fletcher, M., Velasco, C., Wilk, A., Reiss, K., & Rodriguez, P. C.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2013-12-03
- Volume
- 134
- Issue
- 12
- Pages
- 2853-2864
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W1552212814
- Cited by
- 297
- References
- 45
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- green
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- Raber, P. L., Thevenot, P., Sierra, R., Wyczechowska, D., Halle, D., Ramirez, M. E., Ochoa, A. C., Fletcher, M., Velasco, C., Wilk, A., Reiss, K., & Rodriguez, P. C. (2014). Subpopulations of myeloid‐derived suppressor cells impair T cell responses through independent nitric oxide‐related pathways. International Journal of Cancer. https://doi.org/10.1002/ijc.28622
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