相关实验视频

Updated: Jan 9, 2026

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Published on: June 12, 2021

转录因子Zfx调节瘤逃避T细胞杀死在免疫治疗中的过程

Ulrike Kaufmann¹, Joy Wang¹, Marinella G Callow²

¹Department of Translational Oncology, Genentech Inc., South San Francisco, CA, USA.

|December 1, 2025

概括

转录因子指蛋白X连接 (Zfx) 有助于T细胞杀死癌细胞. 丢失Zfx使瘤对免疫疗法产生抵抗力,这表明Zfx是治疗反应的潜在生物标志物.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
遗传学是一个遗传学.

背景情况:

癌症免疫疗法增强T细胞反应,但面临抵抗.
了解瘤细胞抵抗机制对于改善治疗方法至关重要.

研究的目的:

用CRISPR-Cas9查来识别影响T细胞杀死敏感性的瘤特异性基因.
阐明已识别的基因,指蛋白X链 (Zfx) 在癌症免疫疗法耐药性中的作用.

主要方法:

用CRISPR-Cas9进行全基因组查,以确定耐药性基因.
在体外和体内测试以评估Zfx淘汰瘤细胞的T细胞杀死.
ChIP-Seq分析ZFX与亡基因促进体结合的结果.
对人类癌症组织中ZFX表达的分析以及与患者存活率和免疫治疗反应的相关性.

主要成果:

Zfx被确定为一个关键的基因,调节瘤细胞对T细胞杀伤的敏感性.
Zfx淘汰赛瘤细胞表现出对T细胞介导溶解的抗性.
Zfx直接控制着包括Caspase-3在内的亡基因的表达.
在人类癌症中观察到ZFX表达的减少;高ZFX与脏癌症的更好的生存率相关,并在黑色素瘤中对抗PD-1免疫疗法的积极反应.

结论:

通过调节亡,Zfx在调解T细胞杀死瘤细胞方面发挥着至关重要的作用.
Zfx代表了瘤细胞对免疫疗法的内在耐药性的新机制.
Zfx是预测免疫治疗反应的潜在生物标志物,也是克服耐药性的治疗标.

关键词:

瘤学在瘤学方面.

更多相关视频

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Published on: February 24, 2023

相关概念视频

Tumor Immunotherapy

Tumor Immunotherapy

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.

The Tumor Microenvironment

The Tumor Microenvironment

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...

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

Master Transcription Regulators

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

General Transcription Factors

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...

Regulation of Angiogenesis and Blood Supply

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...