相关实验视频

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

一个主要的染色体调节剂决定了瘤细胞对T细胞间接杀伤的抵抗力

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

概括

由于对免疫疗法的理解不足,瘤细胞抵抗免疫疗法. 禁用PBAF染色体重塑剂,如PBRM1,使癌细胞对杀死T细胞敏感,从而提高免疫疗法的有效性.

科学领域:

免疫学
癌症生物学
遗传学

背景情况:

许多人体癌症对免疫疗法具有抗性,限制了治疗的有效性.
驱动瘤细胞对细胞毒性T细胞中介杀伤的精确机制在很大程度上是未知的.
了解这些抵抗机制对于开发更有效的癌症免疫疗法至关重要.

研究的目的:

通过全基因组查,确定瘤细胞对细胞毒性T细胞的抗性.
研究PBAF染色体重塑复合物在免疫治疗耐药性的作用.
探索针对PBAF组件克服治疗耐药性的治疗潜力.

主要方法:

用基因组规模的CRISPR-Cas9查系统地使黑色素瘤细胞中的基因失活.
评估了基因失活的细胞对细胞毒性T细胞杀死的敏感性.
分析基因表达模式和化学激素分泌以应对PBAF组件的不活化.
人类癌症中PBAF成分与T细胞毒性标志物的相关基因表达.

主要成果:

超过100个基因的失活,包括PBAF组件 (PBRM1,ARID2,BRD7),使黑色素瘤细胞对T细胞介导的杀死敏感.
损失PBAF功能增加了瘤细胞对干扰素的敏感性,增加了化学激素的分泌,吸引了T细胞.
禁用PBRM1使得治疗耐药的瘤对免疫疗法产生反应.
在人类癌症中,降低PBRM1和ARID2表达与T细胞毒性基因表达相反相关.

结论:

PBAF染色体重塑复合体是瘤细胞对细胞毒性T细胞敏感性的关键调节剂.
针对PBAF组件,如PBRM1,可以克服某些癌症的免疫疗法耐药性.
这些发现凸显了PBAF作为增强癌症免疫治疗结果的潜在治疗点.

更多相关视频

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

相关概念视频

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...