Prognostic value of diametrically polarized tumor-associated macrophages in multiple myeloma.
Prognostic value of diametrically polarized tumor-associated macrophages in multiple myeloma.
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直径极化肿瘤相关巨噬细胞在多发性骨髓瘤中的预后价值
DOI：
10.18632/oncotarget.22340
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发表时间：
2017-12-22
期刊：
影响因子：
--
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Chen X;Chen J;Zhang W;Sun R;Liu T;Zheng Y;Wu Y
许多临床研究表明，肿瘤相关巨噬细胞（Tumor-associated macrophages, tam）与不同类型实体瘤和淋巴瘤的预后相关。体外实验证明了这些细胞在骨髓瘤细胞存活、血管生成、免疫调节、耐药以及恶性骨髓瘤细胞与微环境相互作用中的作用。在这里，我们研究了TAMs在多发性骨髓瘤（MM）患者中的预后意义。2009年1月至2014年12月，我们通过免疫组织化学染色CD68、iNOS和CD163对240例MM患者的骨髓进行极化功能状态评估。CD68+或CD163+ TAM高密度患者的化疗总有效率低于低密度患者。Kaplan-Meier分析显示，CD163+ TAM低密度患者的无进展生存期（PFS, p = 0.001）和总生存期（OS, p < 0.001）显著高于CD163+ TAM高密度患者。此外，iNOS+和CD163+ tam （iNOS/CD163签名）的联合分析显示，在预测PFS （p < 0.001）和OS （p < 0.001）的患者结局方面，iNOS+和CD163+ tam （iNOS/CD163签名）都具有更大的功效。此外，Cox回归分析发现iNOS+和CD163+ tam是独立的预后因素（p = 0.007, p < 0.001）。这些因素可以与国际分期系统（ISS）相结合，生成患者预后的预测图。我们的研究结果表明，直径极化的tam镶嵌是一个新的独立的预后因素，可以整合到MM的评估和治疗中。
Tumor-associated macrophages (TAMs) are correlated with the prognosis of different types of solid tumors and lymphoma, according to many clinical studies. In vitro experiments have demonstrated the roles of these cells in myeloma cell survival, angiogenesis, immunomodulation, drug resistance, and the interaction between malignant myeloma cells and the microenvironment. Here, we investigated the prognostic significance of TAMs in patients with multiple myeloma (MM). We evaluated the polarized functional status of bone marrow infiltrated by TAMs by immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM from January 2009 to December 2014. The overall response rates to chemotherapy were lower in patients with high CD68+ or CD163+ TAM densities than in those with low densities. Kaplan-Meier analysis showed that the progression-free survival (PFS, p = 0.001) and overall survival (OS, p < 0.001) of patients with low CD163+ TAM density were significantly higher than those of patients with high CD163+ TAM density. Furthermore, combined analysis of iNOS+ and CD163+ TAMs (iNOS/CD163 signature) exhibited greater power in predicting patient outcomes for both PFS (p < 0.001) and OS (p < 0.001). Moreover, Cox regression analysis identified iNOS+ and CD163+ TAMs as independent prognostic factors (p = 0.007, p < 0.001, respectively). These factors could be combined with the international staging system (ISS) to generate a predictive nomogram for patient outcomes. Our findings suggest that the mosaic of diametrically polarized TAMs is a novel independent prognostic factor that could be integrated into the evaluation of and therapy for MM.
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DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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影响因子：
32.4
作者：
Noy, Roy;Pollard, Jeffrey W.
通讯作者：
Pollard, Jeffrey W.
影响因子：
11.4
作者：
Durie, B. G. M.;Harousseau, J-L;Rajkumar, S. V.
通讯作者：
Rajkumar, S. V.
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DOI：
10.1084/jem.20080124
发表时间：
2008-06-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fong CH;Bebien M;Didierlaurent A;Nebauer R;Hussell T;Broide D;Karin M;Lawrence T
通讯作者：
Lawrence T
影响因子：
32.4
作者：
Murray, Peter J.;Allen, Judith E.;Biswas, Subhra K.;Fisher, Edward A.;Gilroy, Derek W.;Goerdt, Sergij;Gordon, Siamon;Hamilton, John A.;Ivashkiv, Lionel B.;Lawrence, Toby;Locati, Massimo;Mantovani, Alberto;Martinez, Fernando O.;Mege, Jean-Louis;Mosser, David M.;Natoli, Gioacchino;Saeij, Jeroen P.;Schultze, Joachim L.;Shirey, Kari Ann;Sica, Antonio;Suttles, Jill;Udalova, Irina;van Ginderachter, Jo A.;Vogel, Stefanie N.;Wynn, Thomas A.
通讯作者：
Wynn, Thomas A.