Origin and pharmacological modulation of tumor-associated regulatory dendritic cells.
Origin and pharmacological modulation of tumor-associated regulatory dendritic cells.
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肿瘤相关调节树突状细胞的起源和药理学调节。
DOI：
10.1002/ijc.28590
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发表时间：
2014-06-01
影响因子：
6.4
通讯作者：
Shurin, Galina V.
中科院分区：
文献类型：
--
作者：
Zhong, Hua;Gutkin, Dmitriy W.;Han, Baohui;Ma, Yang;Keskinov, Anton A.;Shurin, Michael R.;Shurin, Galina V.
免疫调节细胞的促肿瘤活性已被证明在排除免疫监视和限制抗癌疗法的功效方面发挥着重要作用。尽管已经提供了多种方法来消除骨髓源性抑制细胞 (MDSC) 和调节性 T 细胞，但没有关于如何控制肿瘤环境中抑制性树突状细胞 (DC) 积累或功能的数据。尽管癌症中 DC 的免疫抑制功能与未成熟和浆细胞样 DC 相关，但传统 DC (cDC) 如何产生免疫抑制特性的细节仍知之甚少。在这里，我们发现小鼠肺癌的发生与 MDSC 出现之前调节性 DC (regDC) 的快速积累有关。通过体外和体内方法，我们证明了（i）cDC和MDSC都可以在肺癌环境中极化为促肿瘤regDC； (ii) cDC → regDC 极化是由小 Rho GTPase 信号传导介导的，可以通过非细胞毒性剂量的紫杉醇来控制； (iii) 预防 regDC 的出现增加了 DC 疫苗在肺癌中的抗肿瘤潜力。这些发现不仅为骨髓调节细胞家族带来了新的参与者，为癌症治疗提供了新的靶点，而且为低、非细胞毒性剂量的化疗药物的免疫调节能力提供了新的见解。
Protumorigenic activity of immune regulatory cells has been proven to play a major role in precluding immunosurveillance and limiting the efficacy of anticancer therapies. Although several approaches have been offered to deplete myeloid-derived suppressor cells (MDSC) and regulatory T cells, there are no data on how to control suppressive dendritic cell (DC) accumulation or function in the tumor environment. Although immunosuppressive function of DC in cancer was implicated to immature and plasmacytoid DC, details of how conventional DC (cDC) develop immunosuppressive properties remain less understood. Here, we show that the development of lung cancer in mice was associated with fast accumulation of regulatory DC (regDC) prior to the appearance of MDSC. Using the in vitro and in vivo approaches, we demonstrated that (i)both cDC and MDSC could be polarized into protumor regDC in the lung cancer environment; (ii) cDC → regDC polarization was mediated by the small Rho GTPase signaling, which could be controlled by noncytotoxic doses of paclitaxel; and (iii) prevention of regDC appearance increased the antitumor potential of DC vaccine in lung cancer. These findings not only bring new players to the family of myeloid regulatory cells and provide new targets for cancer therapy, but offer novel insights into the immunomodulatory capacity of chemotherapeutic agents used in low, noncytotoxic doses.
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影响因子：
24.3
作者：
Correia, Ana Luisa;Bissell, Mina J.
通讯作者：
Bissell, Mina J.
影响因子：
11.2
作者：
Ozao-Choy J;Ma G;Kao J;Wang GX;Meseck M;Sung M;Schwartz M;Divino CM;Pan PY;Chen SH
通讯作者：
Chen SH
影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
影响因子：
8.7
作者：
Manicassamy S;Pulendran B
通讯作者：
Pulendran B
影响因子：
4.3
作者：
Fu, Bi-mang;He, Xiao-shun;Huang, Jie-fu
通讯作者：
Huang, Jie-fu