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

• K. V. Argyropoulos ^[1] ; M. Pulitzer ^[1] ; S. Perez ^[3] ; P. Korkolopoulou ^[2] ; M. Angelopoulou ^[2] ; C. Baxevanis ^[3] ; M. L. Palomba ^[1] ; M. Siakantaris ^[2]
  1. [1] Memorial Sloan Kettering Cancer Center

     Memorial Sloan Kettering Cancer Center

     Estados Unidos

     
  2. [2] National and Kapodistrian University of Athens

     National and Kapodistrian University of Athens

     Dimos Athens, Grecia

     
  3. [3] Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece

  Mostrar afiliaciones +
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 7, 2020, págs. 1059-1068
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • PurposeCutaneous 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 sup-pressor 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.MethodsTumor-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/-.ResultsMDSC 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). Circulat-ing 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).ConclusionsThis 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