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Tumor-infiltrating and circulating granulocytic myeloid-derived suppressor cells correlate with disease activity and adverse clinical outcomes in mycosis fungoides

  • K. V. ArgyropoulosEmail author
  • M. Pulitzer
  • S. Perez
  • P. Korkolopoulou
  • M. Angelopoulou
  • C. Baxevanis
  • M. L. Palomba
  • M. Siakantaris
Research Article

Abstract

Purpose

Cutaneous T cell lymphomas (CTCL) are rare and histologically diverse lymphoproliferative neoplasms, with mycosis fungoides (MF) representing the most common disease subset. Given the emerging role of myeloid-derived suppressor cells (MDSC) as a clinically applicable biomarker in solid tumors, we sought to investigate the presence of tumor-infiltrating and circulating MDSC in early- and advanced-stage MF patients and evaluate their prognostic significance in patient overall survival.

Methods

Tumor-infiltrating MDSC were assessed immunohistochemically with Arginase-1 in 31 MF and 14 non-MF skin punch biopsies. Circulating MDSC were assessed with flow cytometry in freshly isolated PBMC from 29 MF patients. Granulocytic MDSC (G-MDSC) were defined as CD11b+CD14−CD15+ and monocytic MDSC (M-MDSC) were defined as CD11b+CD14+HLA-DRlow/-.

Results

MDSC infiltration occurred in approximately one-third (35.5%) of CTCL lesions, with a predilection for non-MF lesions (p < 0.05). The predominant morphology of MDSC was granulocytic. Although in MF lesions the presence of MDSC infiltrates did not correlate with clinical stage, it conferred significantly worse overall survival outcomes (p < 0.05). Circulating G-MDSC were significantly higher in MF patients compared to healthy donor controls (p < 0.0001), while M-MDSC did not show any statistically significant difference. G-MDSC were significantly higher in patients with active disease compared to patients who were in partial remission (p < 0.01). As with tumor-infiltrating MDSC, clinical stage did not correlate with circulating G-MDSC levels, while prospective overall survival analysis showed that patients with high levels of circulating G-MDSC have significantly inferior outcomes (p < 0.01).

Conclusions

This study shows that G-MDSC could represent a novel and easily assessable biomarker in MF, which mirrors disease activity and can predict patient subgroups with aggressive clinical features.

Keywords

Cutaneous T-cell Lymphoma Mycosis fungoides Myeloid-derived suppressor cells 

Notes

Acknowledgements

We would like to thank Dr. Katya Manova and the personnel of the Molecular Cytology Core Facility at Memorial Sloan Kettering Cancer Center, as well as the Pathology Core Facility for the help with immunohistochemistry studies.

Author contributions

KVA, SP, CB, MLP and MS conceived and designed the experiments. KVA and SP performed the experiments. KVA and MP evaluated H&E morphology and analyzed the immunohistochemistry data. KVA and SP performed the flow cytometry analysis and statistical analysis. PK, MA, MLP and MS helped in the collection of patient material. KVA wrote the manuscript. MLP and MS reviewed and edited the manuscript.

Funding

This work was supported by The Lymphoma Foundation, the Greenberg Lymphoma Research Award (MSKCC) and the P30 CA008748 MSK Cancer Center Support Grant/Core Grant.

Compliance with ethical standards

Conflict of interest

M.Lia Palomba serves as a consultant for Merck and Pharmcyclics. The rest of the authors have no interest to disclose.

Research involving human participants

Specimen collection was approved by the Memorial Sloan Kettering Cancer Center Institutional Review Board and the National and Kapodistrian University of Athens Bioethics committee.

Informed consent

Patient material was obtained from patients who had previously signed informed consent, in accordance with the Declaration of Helsinki.

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Immunology ProgramMemorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Hematology Department, Laiko General HospitalNational and Kapodistrian University of AthensAthensGreece
  3. 3.Pathology DepartmentMemorial Sloan Kettering Cancer CenterNew YorkUSA
  4. 4.Cancer Immunology and Immunotherapy CenterSaint Savas Cancer HospitalAthensGreece
  5. 5.Pathology DepartmentNational and Kapodistrian University of AthensAthensGreece
  6. 6.Lymphoma ServiceMemorial Sloan Kettering Cancer CenterNew YorkUSA

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