The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth
Open accessAbstract
PurposeMyeloid-derived suppressor cells (MDSC) are a heterogeneous population of immunosuppressive cells that are upregulated in cancer. Little is known about the prevalence and importance of MDSC in pancreas adenocarcinoma (PA).Experimental designPeripheral blood, bone marrow, and tumor samples were collected from pancreatic cancer patients, analyzed for MDSC (CD15+CD11b+) by flow cytometry and compared to cancer-free controls. The suppressive capacity of MDSC (CD11b+Gr-1+) and the effectiveness of MDSC depletion were assessed in C57BL/6 mice inoculated with Pan02, a murine PA, and treated with placebo or zoledronic acid, a potent aminobisphosphonate previously shown to target MDSC. The tumor microenvironment was analyzed for MDSC (Gr1+CD11b+), effector T cells, and tumor cytokine levels.ResultsPatients with PA demonstrated increased frequency of MDSC in the bone marrow and peripheral circulation which correlated with disease stage. Normal pancreas tissue showed no MDSC infiltrate, while human tumors avidly recruited MDSC. Murine tumors similarly recruited MDSC that suppressed CD8+ T cells in vitro and accelerated tumor growth in vivo. Treatment with zoledronic acid impaired intratumoral MDSC accumulation resulting in delayed tumor growth rate, prolonged median survival, and increased recruitment of T cells to the tumor. This was associated with a more robust type 1 response with increased levels of IFN-γ and decreased levels of IL-10.ConclusionsMDSC are important mediators of tumor-induced immunosuppression in pancreatic cancer. Inhibiting MDSC accumulation with zoledronic acid improves the host anti-tumor response in animal studies suggesting that efforts to block MDSC may represent a novel treatment strategy for pancreatic cancer.
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Myeloid-derived-suppressor cells as regulators of the immune system
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Subsets of Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice
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Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver
Costa-Silva, B., Aiello, N. M., Ocean, A. J., Singh, S., Zhang, H., Thakur, B. K., Becker, A., Hoshino, A., Mark, M. T., Molina, H., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3169 · Cited by 2,692
The 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
History of myeloid-derived suppressor cells
Talmadge, J. E., & Gabrilovich, D. I. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3581 · Cited by 1,148
O’Reilly, E. M., Oh, D.-Y., Dhani, N., Renouf, D. J., Lee, M. A., Sun, W., Fisher, G., Hezel, A., Chang, S.-C., Vlahovic, G., et al. (2019) · JAMA Oncology · doi:10.1001/jamaoncol.2019.1588 · Cited by 767
Ugel, S., De Sanctis, F., Mandruzzato, S., & Bronte, V. (2015) · Journal of Clinical Investigation · doi:10.1172/jci80006 · Cited by 559
Metadata
- Authors
- Porembka, M. R., Mitchem, J. B., Belt, B. A., Hsieh, C.-S., Lee, H.-M., Herndon, J., Gillanders, W. E., Linehan, D. C., & Goedegebuure, P.
- Venue
- Cancer Immunology, Immunotherapy
- Published
- 2012-01-04
- Volume
- 61
- Issue
- 9
- Pages
- 1373-1385
- ISSN
- 0340-7004 (ISSN-L)
- 1432-0851
- OpenAlex
- W2008658155
- Cited by
- 277
- References
- 73
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- green
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- Porembka, M. R., Mitchem, J. B., Belt, B. A., Hsieh, C.-S., Lee, H.-M., Herndon, J., Gillanders, W. E., Linehan, D. C., & Goedegebuure, P. (2012). Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth. Cancer Immunology, Immunotherapy. https://doi.org/10.1007/s00262-011-1178-0
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