Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response.
Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response.
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DOI：
10.1038/s41467-023-36826-0
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发表时间：
2023-02-25
影响因子：
16.6
通讯作者：
La Thangue, Nicholas B. B.
中科院分区：
文献类型：
--
作者：
Barczak, Wojciech;Carr, Simon M. M.;Liu, Geng;Munro, Shonagh;Nicastri, Annalisa;Lee, Lian Ni;Hutchings, Claire;Ternette, Nicola;Klenerman, Paul;Kanapin, Alexander;Samsonova, Anastasia;La Thangue, Nicholas B. B.
蛋白质精氨酸甲基转移酶（PRMT）5在多种癌症中过度表达，主转录调节因子E2F1是重要的甲基化靶点。我们已经探索了PRMT5和E2F1在调节非编码基因组中的作用，并在此报告了对长非编码（lnc）RNA基因表达的显著影响。此外，许多MHC I类蛋白相关肽来源于lncRNA基因中的小开放阅读框。PRMT5的药理学抑制或调节E2F1水平定性地改变了肿瘤细胞展示的lncRNA衍生肽抗原的库。当作为离体负载的树突状细胞或从病毒载体表达的树突状细胞呈递给免疫系统时，lncRNA衍生的肽驱动有效的抗原特异性CD8 T淋巴细胞应答，这转化为肿瘤生长的显著延迟。因此，lncRNA基因编码可用作癌症疫苗的免疫原性肽。长链非编码RNA分子是长期以来被认为保持未翻译的RNA转录物。在这项研究中，作者证明某些lncRNA可以翻译成对CD8+ T细胞具有免疫原性的肽，并在小鼠中作为疫苗载体递送时促进抗肿瘤反应。
Protein arginine methyltransferase (PRMT) 5 is over-expressed in a variety of cancers and the master transcription regulator E2F1 is an important methylation target. We have explored the role of PRMT5 and E2F1 in regulating the non-coding genome and report here a striking effect on long non-coding (lnc) RNA gene expression. Moreover, many MHC class I protein-associated peptides were derived from small open reading frames in the lncRNA genes. Pharmacological inhibition of PRMT5 or adjusting E2F1 levels qualitatively altered the repertoire of lncRNA-derived peptide antigens displayed by tumour cells. When presented to the immune system as either ex vivo-loaded dendritic cells or expressed from a viral vector, lncRNA-derived peptides drove a potent antigen-specific CD8 T lymphocyte response, which translated into a significant delay in tumour growth. Thus, lncRNA genes encode immunogenic peptides that can be deployed as a cancer vaccine. Long noncoding RNA molecules are RNA transcripts long thought to remain untranslated. In this study, the authors demonstrate that certain lncRNA can be translated into peptides that are immunogenic to CD8+ T cells and promote anti-tumour responses when delivered as vaccine vectors in mice.
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影响因子：
56.9
作者：
Chen, Jin;Brunner, Andreas-David;Weissman, Jonathan S.
通讯作者：
Weissman, Jonathan S.
癌症免疫疗法。树突状细胞疫苗增加了黑色素瘤新抗原特异性T细胞的广度和多样性。
DOI：
10.1126/science.aaa3828
发表时间：
2015-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carreno BM;Magrini V;Becker-Hapak M;Kaabinejadian S;Hundal J;Petti AA;Ly A;Lie WR;Hildebrand WH;Mardis ER;Linette GP
通讯作者：
Linette GP
影响因子：
64.8
作者：
Hon CC;Ramilowski JA;Harshbarger J;Bertin N;Rackham OJ;Gough J;Denisenko E;Schmeier S;Poulsen TM;Severin J;Lizio M;Kawaji H;Kasukawa T;Itoh M;Burroughs AM;Noma S;Djebali S;Alam T;Medvedeva YA;Testa AC;Lipovich L;Yip CW;Abugessaisa I;Mendez M;Hasegawa A;Tang D;Lassmann T;Heutink P;Babina M;Wells CA;Kojima S;Nakamura Y;Suzuki H;Daub CO;de Hoon MJ;Arner E;Hayashizaki Y;Carninci P;Forrest AR
通讯作者：
Forrest AR
影响因子：
21.3
作者：
Jansson, Martin;Durant, Stephen T.;La Thangue, Nicholas B.
通讯作者：
La Thangue, Nicholas B.
NETMHC-3.0：对于长度为8-11的肽，对人，小鼠和猴子I类亲和力的准确访问预测。
影响因子：
14.9
作者：
Lundegaard, Claus;Lamberth, Kasper;Harndahl, Mikkel;Buus, Soren;Lund, Ole;Nielsen, Morten
通讯作者：
Nielsen, Morten