Immunosuppressive myeloid-derived suppressor cells are increased in splenocytes from cancer patients

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that are increased in the peripheral blood of cancer patients and limit productive immune responses against tumors. Immunosuppressive MDSCs are well characterized in murine splenic tissue and are found at higher frequencies in spleens of tumor-bearing mice. However, no studies have yet analyzed these cells in parallel human spleens. We hypothesized that MDSCs would be increased in the spleens of human cancer patients, similar to tumor-bearing mice. We compared the frequency and function of MDSC subsets in dissociated human spleen from 16 patients with benign pancreatic cysts and 26 patients with a variety of cancers. We found that total MDSCs (Linneg CD11bpos CD33pos HLA-DRneg), granulocytic MDSCs (additional markers CD14neg CD15pos), and monocytic MDSCs (CD14pos CD15neg) were identified in human spleen. The monocytic subset was the most prominent in both spleen and peripheral blood and the granulocytic subset was expanded in the spleen relative to matched peripheral blood samples. Importantly, the frequency of CD15pos MDSCs in the spleen was increased in patients with cancer compared to patients with benign pancreatic cysts and was associated with a significantly increased risk of death and decreased overall survival. Finally, MDSCs isolated from the spleen suppressed T cell responses, demonstrating for the first time the functional capacity of human splenic MDSCs. These data suggest that the human spleen is a potential source of large quantities of cells with immunosuppressive function for future characterization and in-depth studies of human MDSCs.

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Abbreviations

CFSE:

Carboxyfluorescein succinimidyl ester

DMSO:

Dimethyl sulfoxide

H&E:

Hematoxylin and Eosin

MDSC:

Myeloid-derived suppressor cell

MLR:

Mixed-lymphocyte reaction

PBMC:

Peripheral blood mononuclear cells

PBS:

Phosphate-buffered saline

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Acknowledgements

This work was supported by funding provided by the University of Colorado Cancer Center Support Grant (P30CA046934), American Cancer Society 2012 Roaring Fork Valley Postdoctoral Research Award, and the Conner Family Foundation Grant.

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Correspondence to Martin D. McCarter.

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Jordan, K.R., Kapoor, P., Spongberg, E. et al. Immunosuppressive myeloid-derived suppressor cells are increased in splenocytes from cancer patients. Cancer Immunol Immunother 66, 503–513 (2017). https://doi.org/10.1007/s00262-016-1953-z

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Keywords

  • MDSCs
  • Human spleen
  • Immunosuppression
  • Cancer