腫瘍の円形RNAは,暗号ペプチドをコードすることで,抗腫瘍免疫を誘発する
Di Huang1,2, Xiaofeng Zhu1,2, Shuying Ye1,2
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Nature
|December 13, 2023
まとめ
以前はコード化されていないゲノムは,抗腫瘍免疫を刺激する円形RNA (circRNAs) から暗号的抗原を生成することができます. circFAM53Bのような腫瘍特異的なcircRNAは,T細胞の反応を強化し,患者の生存率を改善するために,がんワクチンのために利用できます.
科学分野:
- 免疫学
- 腫瘍学
- 分子生物学
背景:
- 以前は非コードゲノム領域が ペプチドをコードし 暗号的抗原として作用し 適応免疫を刺激することが知られている.
- 抗腫瘍免疫における暗号性抗原の正確な役割とメカニズムは完全に理解されていません.
研究 の 目的:
- 抗腫瘍免疫における神秘的な抗原の重要性とメカニズムを調査する.
- 癌の治療の可能性を評価する.
主な方法:
- 人間の乳がんのサンプルにおけるHLAクラスI (HLA-I) ペプチドームとリボソームの配列測定
- 腫瘍特異的な円形RNA (circRNA) から派生したHLA-I結合の暗号性抗原ペプチドの識別と特徴付け: circFAM53B.
- 乳がんとメラノーマのマウスモデルにおけるcircRNAまたはペプチドワクチンを用いたin vivo研究.
主要な成果:
- 特定されたHLA- I結合の暗号ペプチドは,circFAM53Bによって非正規的に翻訳され,CD4+およびCD8+T細胞をプリミングし,抗腫瘍免疫を誘発した.
- CircFAM53Bの発現は,抗原特異性CD8+T細胞の浸透率の増加と,乳がんとメラノーマ患者の生存率の改善と相関していた.
- マウスにおけるcircFAM53Bまたはそのペプチドの接種は,腫瘍抗原特異の細胞毒性T細胞の浸透を促進し,効果的な腫瘍制御につながった.
結論:
- circRNAsの非正規翻訳は,効果的な抗腫瘍免疫を駆動する強力な暗号抗原を生成することができます.
- 腫瘍特異的なcircRNAは,新しいがん免疫療法とワクチン開発の有望な源です.
関連する概念動画
02:39lncRNA - Long Non-coding RNAs
8.6K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K
01:27Tumor Immunotherapy
529
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
529
01:22MicroRNAs
3.0K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
02:15Experimental RNAi
6.1K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.1K
02:17The Tumor Microenvironment
6.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.6K
01:23RNA Interference
26.0K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.0K