Tumor- and organ-dependent infiltration by myeloid-derived suppressor cells

Ibrahim Younos, Moses Donkor, Traci Hoke, Alicia Dafferner, Holly Samson, Sherry Westphal, James Talmadge

Research output: Contribution to journalArticle

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Abstract

Myeloid-derived suppressor cells (MDSCs) increase during tumor growth and following cytoreductive therapy resulting in immune dysfunction and tumor escape from host control. We report organ- and tumor-specific expansion of MDSCs, differences in their molecular and membrane phenotypes and T-cell suppressive activity. A significant increase in MDSCs was observed within the spleen, peripheral blood (PB), bone marrow (BM), lungs, and livers of mice bearing orthotopic 4T1, but not CI66 mammary tumors. The PB of 4T1 TB mice had the highest frequency of MDSCs (78.6 ± 2.1%). Similarly, the non-parenchymal cells (NPCs) in the tumor tissue, livers and lungs of 4T1 tumor-bearing (TB) mice had an increased MDSCs frequency. Studies into Gr-1 and Ly-6C staining of MDSCs revealed significant increases in CD11b+Gr-1 dullLy-6Chigh and CD11b+Gr-1 brightLy-6Clow subsets. The frequency of MDSCs inversely correlated with the CD3+ T-cell frequency in the spleen, and blood of 4T1 TB mice and was associated with a significant decrease in splenic and NPCs IFN-γ and IL-12 transcript levels, as well as significantly increased levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-10 (IL-10), interleukin-13 (IL-13), arginase-1 (ARG-1), nitric oxide synthase (NOS-2), vascular endothelial growth factor-A (VEGF-A) transcripts. In summary, MDSCs are significantly increased not only in lymphoid organs, but also in parenchymal organs including lungs and livers of TB mice, where they may facilitate metastasis to these organ sites.

Original languageEnglish
Pages (from-to)814-824
Number of pages11
JournalInternational Immunopharmacology
Volume11
Issue number7
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Neoplasms
Lung
Liver
Spleen
Tumor Escape
T-Lymphocytes
Arginase
Stem Cell Factor
Interleukin-13
Myeloid-Derived Suppressor Cells
Granulocyte Colony-Stimulating Factor
Interleukin-12
Granulocyte-Macrophage Colony-Stimulating Factor
Nitric Oxide Synthase
Interleukin-10
Vascular Endothelial Growth Factor A
Bone Marrow
Staining and Labeling
Breast Neoplasms
Neoplasm Metastasis

Keywords

  • Immunosuppression
  • Mammary tumor
  • MDSCs
  • Non-parenchymal cells
  • T-cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Younos, I., Donkor, M., Hoke, T., Dafferner, A., Samson, H., Westphal, S., & Talmadge, J. (2011). Tumor- and organ-dependent infiltration by myeloid-derived suppressor cells. International Immunopharmacology, 11(7), 814-824. https://doi.org/10.1016/j.intimp.2011.02.021

Tumor- and organ-dependent infiltration by myeloid-derived suppressor cells. / Younos, Ibrahim; Donkor, Moses; Hoke, Traci; Dafferner, Alicia; Samson, Holly; Westphal, Sherry; Talmadge, James.

In: International Immunopharmacology, Vol. 11, No. 7, 07.2011, p. 814-824.

Research output: Contribution to journalArticle

Younos, I, Donkor, M, Hoke, T, Dafferner, A, Samson, H, Westphal, S & Talmadge, J 2011, 'Tumor- and organ-dependent infiltration by myeloid-derived suppressor cells', International Immunopharmacology, vol. 11, no. 7, pp. 814-824. https://doi.org/10.1016/j.intimp.2011.02.021
Younos, Ibrahim ; Donkor, Moses ; Hoke, Traci ; Dafferner, Alicia ; Samson, Holly ; Westphal, Sherry ; Talmadge, James. / Tumor- and organ-dependent infiltration by myeloid-derived suppressor cells. In: International Immunopharmacology. 2011 ; Vol. 11, No. 7. pp. 814-824.
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