Genome-wide gain-of-function screening characterized lncRNA regulators for tumor immune response.
Genome-wide gain-of-function screening characterized lncRNA regulators for tumor immune response.
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DOI：
10.1126/sciadv.add0005
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发表时间：
2022-12-09
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
大多数lncrna在肿瘤免疫学中的作用尚不清楚。本项目在与人CD8+ T细胞共培养的黑色素瘤细胞中对9744个lncRNAs进行了CRISPR激活筛选。我们鉴定出16个可能调节肿瘤免疫反应的lncrna。利用肿瘤免疫基因组学数据的进一步综合分析显示，IL10RB-DT和LINC01198与黑色素瘤和乳腺癌的肿瘤免疫反应和生存显著相关。具体来说，IL10RB-DT通过抑制黑色素瘤和乳腺癌细胞中的IFN -γ-JAK-STAT1信号传导和抗原呈递来抑制CD8+ T细胞的活化。另一方面，LINC01198的上调使CD8+ T细胞对肿瘤细胞的杀伤变得敏感。在机制上，LINC01198相互作用并激活NF-κB成分p65，触发黑色素瘤和乳腺癌细胞中的I型和II型干扰素反应。我们的研究系统地描述了参与肿瘤免疫反应的新型lncrna。该项目使用高通量功能获得筛选来鉴定调节癌症免疫反应的非编码基因。
The majority of lncRNAs’ roles in tumor immunology remain elusive. This project performed a CRISPR activation screening of 9744 lncRNAs in melanoma cells cocultured with human CD8+ T cells. We identified 16 lncRNAs potentially regulating tumor immune response. Further integrative analysis using tumor immunogenomics data revealed that IL10RB-DT and LINC01198 are significantly correlated with tumor immune response and survival in melanoma and breast cancer. Specifically, IL10RB-DT suppresses CD8+ T cells activation via inhibiting IFN-γ–JAK–STAT1 signaling and antigen presentation in melanoma and breast cancer cells. On the other hand, LINC01198’s up-regulation sensitizes the killing of tumor cells by CD8+ T cells. Mechanistically, LINC01198 interacts and activates NF-κB component p65 to trigger the type I and type II interferon responses in melanoma and breast cancer cells. Our study systematically characterized novel lncRNAs involved in tumor immune response. This project used a high-throughput gain-of-function screening to identify non-coding genes that regulate cancer immune response.
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影响因子：
28.2
作者：
Gstalder C;Liu D;Miao D;Lutterbach B;DeVine AL;Lin C;Shettigar M;Pancholi P;Buchbinder EI;Carter SL;Manos MP;Rojas-Rudilla V;Brennick R;Gjini E;Chen PH;Lako A;Rodig S;Yoon CH;Freeman GJ;Barbie DA;Hodi FS;Miles W;Van Allen EM;Haq R
通讯作者：
Haq R
影响因子：
32.4
作者：
Dersh D;Phelan JD;Gumina ME;Wang B;Arbuckle JH;Holly J;Kishton RJ;Markowitz TE;Seedhom MO;Fridlyand N;Wright GW;Huang DW;Ceribelli M;Thomas CJ;Lack JB;Restifo NP;Kristie TM;Staudt LM;Yewdell JW
通讯作者：
Yewdell JW
影响因子：
46.9
作者：
Doench JG;Fusi N;Sullender M;Hegde M;Vaimberg EW;Donovan KF;Smith I;Tothova Z;Wilen C;Orchard R;Virgin HW;Listgarten J;Root DE
通讯作者：
Root DE
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
13.6
作者：
Guo W;Wang Y;Yang M;Wang Z;Wang Y;Chaurasia S;Wu Z;Zhang M;Yadav GS;Rathod S;Concha-Benavente F;Fernandez C;Li S;Xie W;Ferris RL;Kammula US;Lu B;Yang D
通讯作者：
Yang D