Myeloid-derived suppressor cell and macrophage exert distinct angiogenic and immunosuppressive effects in breast cancer.
Myeloid-derived suppressor cell and macrophage exert distinct angiogenic and immunosuppressive effects in breast cancer.
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骨髓源性抑制细胞和巨噬细胞在乳腺癌中发挥独特的血管生成和免疫抑制作用
DOI：
10.18632/oncotarget.17013
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发表时间：
2017-08-15
期刊：
影响因子：
--
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Fang Z;Wen C;Chen X;Yin R;Zhang C;Wang X;Huang Y
免疫抑制性肿瘤微环境是阻碍癌症免疫治疗的关键障碍。骨髓源性抑制细胞（MDSC）被认为是免疫抑制的主要参与者。在这项研究中，我们发现，肿瘤浸润MDSC（tiMDSC）的免疫抑制比肿瘤相关的巨噬细胞（TAM）在多个小鼠原位乳腺肿瘤模型。与TAM相比，tiMDSC产生更高水平的促炎因子和更低水平的抗炎因子。此外，tiMDSC优先位于缺氧区域，并且比TAM更促血管生成。与这些功能差异一致，在乳腺癌进展期间观察到从tiMDSC到TAM的转变。此外，在肺中乳腺癌细胞的远端定殖中也注意到了tiMDSC的浸润。总之，我们的研究结果表明，tiMDSC更具促血管生成作用并促进肿瘤发生，而TAM更具免疫抑制作用并促进肿瘤免疫逃避。这项研究表明，选择性靶向TAM可以缓解免疫抑制肿瘤微环境，增强癌症免疫治疗。
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.
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影响因子：
50.3
作者：
Huang Y;Snuderl M;Jain RK
通讯作者：
Jain RK
影响因子：
4.4
作者：
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通讯作者：
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CXCR2 的抑制可显着抑制炎症驱动和自发性肿瘤发生
影响因子：
15.9
作者：
Jamieson, Thomas;Clarke, Mairi;Sansom, Owen J.
通讯作者：
Sansom, Owen J.
影响因子：
20.1
作者：
Bodnar, RJ;Yates, CC;Wells, A
通讯作者：
Wells, A
影响因子：
16.6
作者：
Bronte V;Brandau S;Chen SH;Colombo MP;Frey AB;Greten TF;Mandruzzato S;Murray PJ;Ochoa A;Ostrand-Rosenberg S;Rodriguez PC;Sica A;Umansky V;Vonderheide RH;Gabrilovich DI
通讯作者：
Gabrilovich DI