Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer.
Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer.
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DOI：
10.3390/genes8110308
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发表时间：
2017-11-07
期刊：
影响因子：
3.5
通讯作者：
Wang E
中科院分区：
文献类型：
--
作者：
Han P;Gopalakrishnan C;Yu H;Wang E
免疫细胞的基因调控网络（GRNs）不仅可以表明细胞的同一性，而且可以通过比较它们的GRNs来揭示免疫细胞的动态变化。癌症免疫疗法在过去几年中取得了进展。免疫检查点阻断（即，阻断PD-1、PD-L1或CTLA-4）对一些患有各种晚期癌症的患者显示出持久的临床效果。然而，我们对免疫疗法的认识存在重大差距。为了填补这些空白，我们对关键免疫细胞亚群（即，与癌症免疫治疗相关的B细胞、CD 4、CD 8、CD 8幼稚、CD 8效应记忆、CD 8中央记忆、调节性T、Thelper 1、Thelper 2、Thelp 17和NK（自然杀伤细胞）和DC（树突细胞）细胞。我们发现，血液中这些细胞的大多数GRN都具有关键的重要中枢调节因子，但它们控制细胞类型特异性受体的子网络是不同的，这表明这些免疫细胞亚群之间的转化可能很快，因此它们可以快速响应环境提示。为了了解癌细胞如何向免疫细胞发送分子信号，使其对癌细胞更加友好，我们比较了肿瘤浸润免疫T细胞及其血液中相应免疫细胞的GRNs。我们发现，与血液中相应免疫细胞的GRNs相比，肿瘤浸润免疫T细胞的GRNs的网络尺寸减小。这些结果表明，癌细胞关闭免疫细胞的某些细胞活动是帮助癌细胞逃避宿主免疫系统防御的关键分子机制之一。这些结果突出了T细胞基因工程的可能性，可以打开已被癌细胞关闭的已识别的子网络来对抗肿瘤。
The gene regulatory networks (GRNs) of immune cells not only indicate cell identity but also reveal the dynamic changes of immune cells when comparing their GRNs. Cancer immunotherapy has advanced in the past few years. Immune-checkpoint blockades (i.e., blocking PD-1, PD-L1, or CTLA-4) have shown durable clinical effects on some patients with various advanced cancers. However, major gaps in our knowledge of immunotherapy have been recognized. To fill these gaps, we conducted a systematic analysis of the GRNs of key immune cell subsets (i.e., B cell, CD4, CD8, CD8 naïve, CD8 Effector memory, CD8 Central Memory, regulatory T, Thelper1, Thelper2, Thelp17, and NK (Nature killer) and DC (Dendritic cell) cells associated with cancer immunologic therapies. We showed that most of the GRNs of these cells in blood share key important hub regulators, but their subnetworks for controlling cell type-specific receptors are different, suggesting that transformation between these immune cell subsets could be fast so that they can rapidly respond to environmental cues. To understand how cancer cells send molecular signals to immune cells to make them more cancer-cell friendly, we compared the GRNs of the tumor-infiltrating immune T cells and their corresponding immune cells in blood. We showed that the network size of the tumor-infiltrating immune T cells’ GRNs was reduced when compared to the GRNs of their corresponding immune cells in blood. These results suggest that the shutting down certain cellular activities of the immune cells by cancer cells is one of the key molecular mechanisms for helping cancer cells to escape the defense of the host immune system. These results highlight the possibility of genetic engineering of T cells for turning on the identified subnetworks that have been shut down by cancer cells to combat tumors.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
DOI：
10.1109/tvcg.2014.2346248
发表时间：
2014-12
影响因子：
5.2
作者：
Lex A;Gehlenborg N;Strobelt H;Vuillemot R;Pfister H
通讯作者：
Pfister H
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
DOI：
10.1126/science.aad0501
发表时间：
2016-04-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tirosh I;Izar B;Prakadan SM;Wadsworth MH 2nd;Treacy D;Trombetta JJ;Rotem A;Rodman C;Lian C;Murphy G;Fallahi-Sichani M;Dutton-Regester K;Lin JR;Cohen O;Shah P;Lu D;Genshaft AS;Hughes TK;Ziegler CG;Kazer SW;Gaillard A;Kolb KE;Villani AC;Johannessen CM;Andreev AY;Van Allen EM;Bertagnolli M;Sorger PK;Sullivan RJ;Flaherty KT;Frederick DT;Jané-Valbuena J;Yoon CH;Rozenblatt-Rosen O;Shalek AK;Regev A;Garraway LA
通讯作者：
Garraway LA
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS