Elevated levels of polymorphonuclear myeloid-derived suppressor cells in patients
with glioblastoma highly express S100A8/9 and arginase and suppress T cell
function
#MMPMID27006175
Gielen PR
; Schulte BM
; Kers-Rebel ED
; Verrijp K
; Bossman SA
; Ter Laan M
; Wesseling P
; Adema GJ
Neuro Oncol
2016[Sep]; 18
(9
): 1253-64
PMID27006175
show ga
BACKGROUND: Gliomas are primary brain tumors that are associated with a poor
prognosis. The introduction of new treatment modalities (including immunotherapy)
for these neoplasms in the last 3 decades has resulted in only limited
improvement in survival. Gliomas are known to create an immunosuppressive
microenvironment that hampers the efficacy of (immuno)therapy. One component of
this immunosuppressive environment is the myeloid-derived suppressor cell (MDSC).
METHODS: We set out to analyze the presence and activation state of MDSCs in
blood (n = 41) and tumor (n = 20) of glioma patients by measuring S100A8/9 and
arginase using flow cytometry and qPCR. Inhibition of T cell proliferation and
cytokine production after stimulation with anti-CD3/anti-CD28 coated beads was
used to measure in vitro MDSC suppression capacity. RESULTS: We report a trend
toward a tumor grade-dependent increase of both monocytic (M-) and
polymorphonuclear (PMN-) MDSC subpopulations in the blood of patients with
glioma. M-MDSCs of glioma patients have increased levels of intracellular
S100A8/9 compared with M-MDSCs in healthy controls (HCs). Glioma patients also
have increased S100A8/9 serum levels, which correlates with increased arginase
activity in serum. PMN-MDSCs in both blood and tumor tissue demonstrated high
expression of arginase. Furthermore, we assessed blood-derived PMN-MDSC function
and showed that these cells have potent T cell suppressive function in vitro.
CONCLUSIONS: These data indicate a tumor grade-dependent increase of MDSCs in the
blood of patients with a glioma. These MDSCs exhibit an increased activation
state compared with MDSCs in HCs, independent of tumor grade.
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