High-density neutrophils in MGUS and multiple myeloma are dysfunctional and immune-suppressive due to increased STAT3 downstream signaling.
Sci Rep
; 10(1): 1983, 2020 02 06.
Article
in En
| MEDLINE
| ID: mdl-32029833
ABSTRACT
To understand neutrophil impairment in the progression from MGUS through active MM, we investigated the function of mature, high-density neutrophils (HDNs), isolated from peripheral blood. In 7 MM, 3 MGUS and 3 healthy subjects by gene expression profile, we identified a total of 551 upregulated and 343 downregulated genes in MM-HDN, involved in chemokine signaling pathway and FC-gamma receptor mediated phagocytosis conveying in the activation of STAT proteins. In a series of 60 newly diagnosed MM and 30 MGUS patients, by flow-cytometry we found that HDN from MM, and to a lesser extend MGUS, had an up-regulation of the inducible FcγRI (also known as CD64) and a down-regulation of the constitutive FcγRIIIa (also known as CD16) together with a reduced phagocytic activity and oxidative burst, associated to increased immune-suppression that could be reverted by arginase inhibitors in co-culture with lymphocytes. In 43 consecutive newly-diagnosed MM patients, who received first-line treatment based on bortezomib, thalidomide and dexamethasone, high CD64 could identify at diagnosis patients with inferior median overall survival (39.5 versus 86.7 months, p = 0.04). Thus, HDNs are significantly different among healthy, MGUS and MM subjects. In both MGUS and MM neutrophils may play a role in supporting both the increased susceptibility to infection and the immunological dysfunction that leads to tumor progression.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monoclonal Gammopathy of Undetermined Significance
/
Signal Transduction
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Disease Susceptibility
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STAT3 Transcription Factor
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Multiple Myeloma
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Neutrophils
Type of study:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Sci Rep
Year:
2020
Document type:
Article
Affiliation country:
Italia