Functional characterization of human Cd33+ and Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines.
Functional characterization of human Cd33+ and Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines.
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DOI：
10.1186/1479-5876-9-90
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发表时间：
2011-06-09
影响因子：
7.4
通讯作者：
Epstein AL
中科院分区：
文献类型：
--
作者：
Lechner MG;Megiel C;Russell SM;Bingham B;Arger N;Woo T;Epstein AL
肿瘤免疫耐受可来源于抑制细胞群体的募集，包括髓系来源的抑制细胞(MDSC)。在癌症患者中，MDSC的积聚与肿瘤负担的增加相关，但MDSC的诱导机制仍不清楚。本研究采用体外共培养的方法，检测了人肿瘤细胞系从健康供者PBMC中诱导MDSC的能力。然后对这些人的MDSC进行了形态、表型、基因表达和功能的鉴定。在检测的100多个肿瘤细胞系中，45个产生了典型的CD33+HLA-DRlowLineLage-MDSC，其中宫颈、卵巢、结直肠、肾细胞和头颈癌细胞的诱导频率较高。除乳腺癌外(0/9，与激素和HER2状态无关)，所有肿瘤类型的癌细胞株均可诱导CD33+MDSC。进一步检查发现，这些和其他罕见的CD33+MDSC产生的第二个亚群的特征是CD11b+CD33lowHLA-DRlowLineage-。基因和蛋白表达、抗体中和和细胞因子诱导研究表明，CD33+MDSC的诱导依赖于IL-1β、IL-6、肿瘤坏死因子α、血管内皮生长因子和GM-CSF的过度表达，而CD11b+MDSC的诱导与Flt3L和转化生长因子β的过度表达有关。在形态上，CD33+和CD11b+MDSC亚群均表现为未成熟的髓系细胞，iNOS、NADPH氧化酶和精氨酸酶-1基因表达显著上调。此外，转录因子HIF1α、STAT3和C/EBPβ的表达增加将MDSC与正常对照区分开来。这些研究证实了实体瘤诱导MDSC的普遍性，并鉴定了两个不同的MDSC亚群：CD33+HIF1HIF1α+/STAT3+和CD11b+HLADRlowC/EBPβ+，这将为开发新的肿瘤免疫治疗诊断和治疗试剂奠定基础。
Tumor immune tolerance can derive from the recruitment of suppressor cell populations, including myeloid-derived suppressor cells (MDSC). In cancer patients, MDSC accumulation correlates with increased tumor burden, but the mechanisms of MDSC induction remain poorly understood. This study examined the ability of human tumor cell lines to induce MDSC from healthy donor PBMC using in vitro co-culture methods. These human MDSC were then characterized for morphology, phenotype, gene expression, and function. Of over 100 tumor cell lines examined, 45 generated canonical CD33+HLA-DRlowLineage- MDSC, with high frequency of induction by cervical, ovarian, colorectal, renal cell, and head and neck carcinoma cell lines. CD33+ MDSC could be induced by cancer cell lines from all tumor types with the notable exception of those derived from breast cancer (0/9, regardless of hormone and HER2 status). Upon further examination, these and others with infrequent CD33+ MDSC generation were found to induce a second subset characterized as CD11b+CD33lowHLA-DRlowLineage-. Gene and protein expression, antibody neutralization, and cytokine-induction studies determined that the induction of CD33+ MDSC depended upon over-expression of IL-1β, IL-6, TNFα, VEGF, and GM-CSF, while CD11b+ MDSC induction correlated with over-expression of FLT3L and TGFβ. Morphologically, both CD33+ and CD11b+ MDSC subsets appeared as immature myeloid cells and had significantly up-regulated expression of iNOS, NADPH oxidase, and arginase-1 genes. Furthermore, increased expression of transcription factors HIF1α, STAT3, and C/EBPβ distinguished MDSC from normal counterparts. These studies demonstrate the universal nature of MDSC induction by human solid tumors and characterize two distinct MDSC subsets: CD33+HLA-DRlowHIF1α+/STAT3+ and CD11b+HLA-DRlowC/EBPβ+, which should enable the development of novel diagnostic and therapeutic reagents for cancer immunotherapy.
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影响因子：
4.4
作者：
de Kleer, Isme;Vercoulen, Yvonne;Prakken, Berent
通讯作者：
Prakken, Berent
DOI：
10.4049/jimmunol.1000901
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lechner MG;Liebertz DJ;Epstein AL
通讯作者：
Epstein AL
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：
37.3
作者：
Huang WL;Yeh HH;Lin CC;Lai WW;Chang JY;Chang WT;Su WC
通讯作者：
Su WC
影响因子：
11.2
作者：
Ko JS;Rayman P;Ireland J;Swaidani S;Li G;Bunting KD;Rini B;Finke JH;Cohen PA
通讯作者：
Cohen PA