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2017 ; 8
(33
): 54173-54186
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Myeloid-derived suppressor cell and macrophage exert distinct angiogenic and
immunosuppressive effects in breast cancer
#MMPMID28903332
Fang Z
; Wen C
; Chen X
; Yin R
; Zhang C
; Wang X
; Huang Y
Oncotarget
2017[Aug]; 8
(33
): 54173-54186
PMID28903332
show ga
The immunosuppressive tumor microenvironment is a key obstacle to hinder a cancer
immunotherapy. Myeloid-derived suppressor cells (MDSCs) have been considered as a
major player in immunosuppression. In this study, we find that tumor-infiltrating
MDSCs (tiMDSCs) are less immunosuppressive than tumor-associated macrophages
(TAMs) in multiple murine orthotopic breast tumor models. Compared to TAMs,
tiMDSCs produce higher levels of pro-inflammatory factors and lower levels of
anti-inflammatory factors. Furthermore, tiMDSCs are preferentially located in
hypoxic areas and are more pro-angiogenic than TAMs. Consistent with these
functional disparities, a shift from tiMDSCs to TAMs is observed during the
progression of breast cancer. Moreover, infiltration of tiMDSCs is also noted in
distal colonization of breast cancer cells in the lung. Taken together, our
findings indicate that tiMDSCs are more pro-angiogenic and promote tumor
initiation, while TAMs are more immunosuppressive and facilitate tumor immune
evasion. This study suggests that selectively targeting on TAMs could alleviate
the immunosuppressive tumor microenvironment and potentiate cancer immunotherapy.