関連する実験動画

Updated: Feb 16, 2026

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells

Published on: February 22, 2020

主要なクロマチンの調節剤は,T細胞による殺傷に対する腫瘍細胞の抵抗性を決定する

Deng Pan¹, Aya Kobayashi^1,2, Peng Jiang³

¹Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Science (New York, N.Y.)

|January 6, 2018

まとめ

腫瘍細胞は,十分に理解されていないメカニズムのために免疫療法に抵抗します. PBRM1のようなPBAF染色体改造剤を非活性化すると,T細胞殺菌に対するがん細胞の感受性を高め,免疫療法の効果を高めます.

科学分野:

免疫学
癌生物学
遺伝学

背景:

多くのヒトの癌は免疫療法に抵抗し,治療の有効性を制限する.
細胞毒性T細胞媒介による殺戮に対する腫瘍細胞の抵抗を駆動する正確なメカニズムは,ほとんど不明である.
これらの抵抗メカニズムの理解はより効果的ながん免疫療法の開発に不可欠です

研究の目的:

細胞毒性T細胞に対する腫瘍細胞抵抗に関与する遺伝子と経路を全ゲノムスクリーンを用いて特定する.
免疫療法への抵抗を媒介するPBAF染色体改造複合体の役割を調査する.
治療抵抗を克服するためにPBAFの成分を標的とした治療の可能性を探求する.

主な方法:

ゲノムスケールのCRISPR- Cas9スクリーニングを使用して,メラノーマ細胞の遺伝子を体系的に無効化しました.
細胞毒性T細胞による殺戮に対する遺伝子不活性化細胞の感受性を評価した.
PBAF成分不活性化への反応として遺伝子発現パターンとケモカイン分泌を分析した.
人間の癌におけるT細胞細胞毒性マーカーとPBAF成分の相関遺伝子発現.

主要な成果:

PBAF成分 (PBRM1,ARID2,BRD7) を含む100以上の遺伝子の不活性化により,T細胞媒介による殺傷に敏感になったメラノーマ細胞.
PBAFの機能の喪失は,腫瘍細胞のインターフェロン・ガンマに対する感受性を高め,T細胞を惹きつけるケモカインの分泌を増加させた.
PBRM1の無活性化により,治療に抵抗する腫瘍が免疫療法に反応した.
PBRM1とARID2の発現の低下は,ヒトがんにおけるT細胞細胞毒性遺伝子発現と逆相関している.

結論:

PBAF染色体改造複合体は,細胞毒性T細胞に対する腫瘍細胞の感受性の主要な調節体である.
PBRM1などのPBAF成分をターゲットにすることで,特定のがんの免疫療法抵抗を克服することができます.
これらの発見は,PBAFをがん免疫療法の成果を向上させる潜在的な治療目標として強調しています.

さらに関連する動画

Native Chromatin Immunoprecipitation Using Murine Brain Tumor Neurospheres

Native Chromatin Immunoprecipitation Using Murine Brain Tumor Neurospheres

Published on: January 29, 2018

Chromatin Immunoprecipitation ChIP in Mouse T-cell Lines

Chromatin Immunoprecipitation ChIP in Mouse T-cell Lines

Published on: June 17, 2017

関連する概念動画

Chromatin Structure Regulates pre-mRNA Processing

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...

Chromatin Position Affects Gene Expression

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...

Spreading of Chromatin Modifications

Spreading of Chromatin Modifications

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...

pH Regulation in Cells

pH Regulation in Cells

pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...

Chromatin Packaging

Chromatin Packaging

Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter?
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order...

Chromatin Modification in iPS Cells

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...