Τίτλος:
Tumor-infiltrating and circulating granulocytic myeloid-derived suppressor cells correlate with disease activity and adverse clinical outcomes in mycosis fungoides
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2019, Federación de Sociedades Españolas de Oncología (FESEO).
Συγγραφείς:
Argyropoulos, K.V.
Pulitzer, M.
Perez, S.
Korkolopoulou, P.
Angelopoulou, M.
Baxevanis, C.
Palomba, M.L.
Siakantaris, M.
Περιοδικό:
Clinical and Translational Oncology
Λέξεις-κλειδιά:
arginase 1; biological marker; CD11b antigen; CD14 antigen; CD15 antigen; protein bcl 6; transcription factor FOXP3; transcription factor GATA 3; CD11b antigen; CD15 antigen; HLA DR antigen; lipopolysaccharide receptor, adverse outcome; Article; cell infiltration; cryopreservation; disease activity; flow cytometry; histology; human; human tissue; immunohistochemistry; mycosis fungoides; myeloid-derived suppressor cell; outcome assessment; overall survival; punch biopsy; skin biopsy; suppressor cell; survival analysis; T lymphocyte; T lymphocyte activation; tissue section; cancer staging; cell count; female; granulocyte; male; metabolism; monocyte; mycosis fungoides; myeloid-derived suppressor cell; pathology; prognosis; skin tumor; survival rate, CD11b Antigen; Cell Count; Female; Flow Cytometry; Granulocytes; HLA-DR Antigens; Humans; Immunohistochemistry; Lewis X Antigen; Lipopolysaccharide Receptors; Male; Monocytes; Mycosis Fungoides; Myeloid-Derived Suppressor Cells; Neoplasm Staging; Prognosis; Skin Neoplasms; Survival Rate
DOI:
10.1007/s12094-019-02231-7
