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Tsubaki T
; Kadonosono T
; Sakurai S
; Shiozawa T
; Goto T
; Sakai S
; Kuchimaru T
; Sakamoto T
; Watanabe H
; Kondoh G
; Kizaka-Kondoh S
Oncotarget
2018[Feb]; 9
(13
): 11209-11226
PMID29541408
show ga
The immunosuppressive tumor microenvironment is a hallmark of cancer.
Myeloid-derived suppressor cells (MDSCs) are CD11b(+) Gr-1(+) tumor-infiltrating
immature myeloid cells that strongly mediate tumor immunosuppression. The
CD11b(+) Gr-1(+) cells are a heterogeneous cell population, and the impacts of
each subpopulation on tumor progression are not yet completely understood. In the
present study, we identified a novel subpopulation of CD11b(+) Gr-1(+) cells from
murine lung carcinoma tumors according to their strongly adherent abilities.
Although strong adherent activity is a unique property of macrophages, their
marker expression patterns are similar to those of MDSCs; thus, we named this
novel subpopulation MDSC-like adherent cells (MLACs). Unlike known MDSCs, MLACs
lack the ability to suppress cytotoxic T lymphocytes and differentiate into
tumor-associated macrophages (TAMs), but could still directly facilitate tumor
growth and angiogenesis through secreting CCL2, CXCL1/2/5, PAI-1, MMPs, and
VEGFA. Furthermore, MLACs recruited MDSCs via the secretion of CCL2/5 and
CXCL1/2/5, thereby enhancing the immunosuppressive tumor microenvironment and
promoting TAMs-mediated tumor progression. Our findings suggest that MLACs may
function as an initiator of the immunosuppressive tumor microenvironment and
highlight a new therapeutic target to prevent the onset or delay malignant
progression.
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