CD45(+)CD33(low)CD11b(dim) myeloid-derived suppressor cells suppress CD8(+) T cell activity via the IL-6/IL-8-arginase I axis in human gastric cancer.
CD45(+)CD33(low)CD11b(dim) myeloid-derived suppressor cells suppress CD8(+) T cell activity via the IL-6/IL-8-arginase I axis in human gastric cancer.
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DOI：
10.1038/s41419-018-0803-7
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发表时间：
2018-07-09
影响因子：
9
通讯作者：
Zhuang Y
中科院分区：
文献类型：
--
作者：
Mao FY;Zhao YL;Lv YP;Teng YS;Kong H;Liu YG;Wu XL;Hao CJ;Chen W;Duan MB;Han B;Ma Q;Wang TT;Peng LS;Zhang JY;Cheng P;Su CY;Fu XL;Zou QM;Guo G;Guo XL;Zhuang Y
骨髓源性抑制细胞（MDSC）是促肿瘤反应的重要组成部分。MDSC的表型和机制是异质性的，需要在胃癌（GC）患者中进行更精确的表征。在这里，我们已经确定了一个新的子集的CD 45 + CD 33 lowCD 11bdim MDSCs在外周血中的胃癌患者相比，健康人。CD 45 + CD 33 lowCD 11bdim MDSC在形态上类似于中性粒细胞，并表达高水平的中性粒细胞标志物CD 66 b。循环中CD 45 + CD 33 lowCD 11bdim MDSC通过抑制CD 8 + T细胞增殖以及干扰素-γ（IFN-γ）和颗粒酶B（GrB）的产生而有效抑制CD 8 + T细胞活性。胃癌患者外周血中CD 45 + CD 33 lowCD 11bdim MDSCs比例与IFN-γ+ CD 8 + T细胞比例呈负相关。GC患者血清来源的IL-6和IL-8通过PI 3 K-AKT信号通路激活并诱导CD 45 + CD 33 lowCD 11bdim MDSC表达CD 45 + CD 33 lowCD 11bdim。该途径有助于CD 8 + T细胞抑制，因为其通过IL-6/IL-8-β-D-半乳糖苷酶I轴的阻断而被部分拯救。外周血CD 45 + CD 33 lowCD 11bdim MDSC以及IL-6、IL-8和IL-8酶I血清水平与GC进展呈正相关，与患者总生存率呈负相关。总之，我们的研究结果强调，一个亚群的嗜酸性CD 45 + CD 33 lowCD 11bdim MDSCs功能免疫抑制和激活通过IL-6/IL-8-β-淀粉酶I轴在胃癌患者。
Myeloid-derived suppressor cells (MDSCs) are a prominent component of the pro-tumoral response. The phenotype of and mechanisms used by MDSCs is heterogeneous and requires more precise characterization in gastric cancer (GC) patients. Here, we have identified a novel subset of CD45+CD33lowCD11bdim MDSCs in the peripheral blood of GC patients compared to healthy individuals. CD45+CD33lowCD11bdim MDSCs morphologically resembled neutrophils and expressed high levels of the neutrophil marker CD66b. Circulating CD45+CD33lowCD11bdim MDSCs effectively suppressed CD8+ T cells activity through the inhibition of CD8+ T cell proliferation and interferon-γ (IFN-γ) and granzyme B (GrB) production. The proportion of CD45+CD33lowCD11bdim MDSCs also negatively correlated with the proportion of IFN-γ+CD8+ T cell in the peripheral blood of GC patients. GC patient serum-derived IL-6 and IL-8 activated and induced CD45+CD33lowCD11bdim MDSCs to express arginase I via the PI3K-AKT signaling pathway. This pathway contributed to CD8+ T cell suppression as it was partially rescued by the blockade of the IL-6/IL-8-arginase I axis. Peripheral blood CD45+CD33lowCD11bdim MDSCs, as well as IL-6, IL-8, and arginase I serum levels, positively correlated with GC progression and negatively correlated with overall patient survival. Altogether, our results highlight that a subset of neutrophilic CD45+CD33lowCD11bdim MDSCs is functionally immunosuppressive and activated via the IL-6/IL-8-arginase I axis in GC patients.
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影响因子：
6.4
作者：
Rotondo, Rita;Barisione, Gaia;Barbieri, Ottavia
通讯作者：
Barbieri, Ottavia
影响因子：
20.3
作者：
Movahedi, Kiavash;Guilliams, Martin;Van Ginderachter, Jo A.
通讯作者：
Van Ginderachter, Jo A.
影响因子：
20.3
作者：
Munder, M;Mollinedo, F;Modolell, M
通讯作者：
Modolell, M
影响因子：
3.7
作者：
SANDER, B;CARDELL, S;MOLLER, E
通讯作者：
MOLLER, E
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影响因子：
17.1
作者：
Wu H;Zhen Y;Ma Z;Li H;Yu J;Xu ZG;Wang XY;Yi H;Yang YG
通讯作者：
Yang YG