Suppressive role of myeloid-derived suppressor cells (MDSCs) in the microenvironment of breast cancer and targeted immunotherapies.
Suppressive role of myeloid-derived suppressor cells (MDSCs) in the microenvironment of breast cancer and targeted immunotherapies.
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骨髓源性抑制细胞（MDSC）在乳腺癌微环境和靶向免疫治疗中的抑制作用
DOI：
10.18632/oncotarget.11352
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发表时间：
2016-09-27
期刊：
影响因子：
--
通讯作者：
Gong W
中科院分区：
文献类型：
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作者：
Shou D;Wen L;Song Z;Yin J;Sun Q;Gong W
髓源性抑制细胞（myelloid -derived suppressor cells, MDSCs）在促进肿瘤生长和转移中起着关键作用，甚至可以降低免疫治疗的疗效。在乳腺癌中，MDSCs主要被乳腺癌细胞募集，形成有利于肿瘤的微环境，抑制抗肿瘤免疫反应。此外，MDSCs可以直接与乳腺癌细胞发生反应。在本文中，我们描述了几种在乳腺癌中募集MDSCs的方法，包括乳腺癌细胞源性细胞因子和趋化因子。MDSCs在募集过程中的细胞内通路分为STAT3- nf -κB-IDO通路、STAT3/IRF-8通路和PTEN/Akt通路。MDSCs作用于T细胞和NK细胞抑制机体免疫，并通过IL-6反式信号直接促进乳腺癌的发生。我们进一步描述了针对MDSCs的乳腺癌免疫疗法，其分类为：阻止MDSCs的形成，消除MDSCs，减少MDSCs的产物。此外，mdsc靶向免疫疗法增强了其他免疫疗法的效果。鉴于mdscs在乳腺癌恶性行为中具有重要的作用，并且可以通过多种策略进行抑制，我们相信mdscs靶向免疫治疗在未来具有广阔的前景。
Myeloid-derived suppressor cells (MDSCs) play a pivotal role in promoting tumor growth and metastasis and can even decrease the efficacy of immunotherapy. In breast cancer, MDSCs are recruited mainly by breast cancer cells to form a tumor-favoring microenvironment to suppress the anti-tumor immune response. In addition, MDSCs can react directly with breast cancer cells. In this paper, we describe several ways to recruit MDSCs in breast cancer, including breast cancer cell-derived cytokines and chemokines. The intracellular pathways in MDSCs during recruitment are classified as the STAT3-NF-κB-IDO pathway, the STAT3/IRF-8 pathway and the PTEN/Akt pathway. MDSCs act on T cells and NK cells to suppress the body's immunity, and via IL-6 trans-signaling, promote breast cancer directly. We further describe MDSC-targeted immune therapies for breast cancer, which are classified as: preventing the formation of MDSCs, eliminating MDSDCs, and reducing the products of MDSCs. Furthermore, MDSC-targeted immunotherapy potentiates the effect of the other immunotherapies. Based on the facts that MSDCs have significant roles in breast cancer malignant behaviors and can be suppressed by various strategies, we do believe MDSC-targeted immunotherapy presents a broad prospect in the future.