Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity.
Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity.
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DOI：
10.1007/s00262-010-0855-8
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Ostrand-Rosenberg S
中科院分区：
文献类型：
--
作者：
Ostrand-Rosenberg S
髓系来源的抑制细胞(MDSC)聚集在大多数癌症患者和患癌症的实验动物中。它们在对促炎介质的反应中积聚，并使用各种机制来阻断先天和获得性抗肿瘤免疫。由于MDSC在阻止免疫反应中的关键作用，它是免疫治疗的战略障碍，需要激活宿主的细胞介导的和天然的免疫反应。在简要描述了诱导MDSC积聚的因素之后，本文综述了MDSC用来抑制CD4+和CD8+T细胞激活的两种新发现的机制。第一种机制是MDSC对半胱氨酸的隔离，半胱氨酸是一种T细胞无法从头合成并需要激活的氨基酸。第二种机制是MDSC下调L-选择素的表达。T细胞必须具有L选择的高表型，才能聚集到淋巴和炎症部位，在那里它们遇到抗原并被激活。通过下调T细胞上的L-选择素，MDSC扰乱了T细胞的转运模式，从而抑制了T细胞的激活。鉴于调控MDSC积聚的条件的复杂性和MDSC使用的抑制机制的多样性，了解哪些条件和机制是主导的，以便针对单个患者的MDSC积聚和/或活性，将MDSC诱导的免疫抑制降至最低，这是至关重要的。
Myeloid-derived suppressor cells (MDSC) accumulate in most cancer patients and experimental animals with cancer. They accumulate in response to pro-inflammatory mediators and they use a variety of mechanisms to block both innate and adaptive antitumor immunity. Because of their critical role in obstructing immune responses, MDSC are a strategic obstacle to immunotherapies that require activation of the host’s cell-mediated and innate immune responses. Following a brief description of the factors that induce MDSC accumulation, this article reviews two newly discovered mechanisms that MDSC use to suppress the activation of CD4+ and CD8+ T cells. The first mechanism is MDSC sequestration of cysteine, an amino acid that T cells are unable to synthesize de novo and that they require for activation. The second mechanism is MDSC-mediated down-regulation of L-selectin. T cells must have an L-selectinhigh phenotype to home to lymph nodes and inflammatory sites where they encounter antigen and are activated. By down-regulating L-selectin on T cells, MDSC perturb T cell trafficking patterns and thereby inhibit T cell activation. Given the complexity of conditions that regulate MDSC accumulation and the variety of suppressive mechanisms used by MDSC, it is essential to understand which conditions and mechanisms are dominant so MDSC accumulation and/or activity can be targeted in individual patients to minimize MDSC-induced immune suppression.
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影响因子：
5.5
作者：
Bunt, Stephanie K.;Clements, Virginia K.;Ostrand-Rosenberg, Suzanne
通讯作者：
Ostrand-Rosenberg, Suzanne
影响因子：
11.2
作者：
Bunt, Stephanie K.;Yang, Linglin;Ostrand-Rosenberg, Suzanne
通讯作者：
Ostrand-Rosenberg, Suzanne
DOI：
10.1084/jem.20080132
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cheng P;Corzo CA;Luetteke N;Yu B;Nagaraj S;Bui MM;Ortiz M;Nacken W;Sorg C;Vogl T;Roth J;Gabrilovich DI
通讯作者：
Gabrilovich DI
DOI：
10.4049/jimmunol.0804253
发表时间：
2009-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hanson EM;Clements VK;Sinha P;Ilkovitch D;Ostrand-Rosenberg S
通讯作者：
Ostrand-Rosenberg S
影响因子：
5.4
作者：
Castellani, Patrizia;Angelini, Giovanna;Rubartelli, Anna
通讯作者：
Rubartelli, Anna