由内源性逆转录病毒元素捕获蛋白质形成瘤细胞衰老和下游免疫信号
Reddick R Walker1,2, Katherine B Chiappinelli1,2
1Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, District of Columbia.
Cancer research
|August 7, 2023
概括
肺状细胞癌 (LUSC) 衰老促进免疫抑制. 一个KLF5激活的HERVH-CALB1开关增加了calbindin,减少了中性粒细胞的招募,并改善了抗癌免疫力.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 肺状细胞癌 (LUSC) 中的细胞衰老会产生免疫抑制的瘤微环境,阻碍化疗和免疫疗法的有效性.
- 与衰老相关的分泌途径通过招募抑制性免疫细胞来促进这种免疫抑制.
研究的目的:
- 在LUSC中识别绕过细胞衰老的分子机制.
- 调查内源逆元素 (ERE) 在调节瘤免疫力中的作用.
主要方法:
- 对转录因子介导的基因表达的分析.
- 研究人类内源逆转录病毒 (HERV) 序列及其在基因转录中的作用.
- 评估calbindin蛋白表达及其对LUSC细胞中化学生产和免疫细胞招募的影响.
主要成果:
- 鉴定了一种转录因子激活的分子开关,导致calbindin蛋白表达的增加.
- 在CALB1基因上游的一个人体内源逆转录病毒 (HERV) 序列 (HERVH) 通过蛋白质捕获促进了化学 HERVH-CALB1 转录的形成.
- 结合HERVH序列的KLF5转录因子驱动了这种转录活动.
- 增加卡尔宾丁的表达减少了CXCL8化学激素的产生和随后的中性粒细胞在LUSC细胞中的招募.
结论:
- 通过HERVH介导的CALB1外是一种新的机制,EREs通过它调节LUSC的抗瘤免疫力.
- 这一途径为克服衰老驱动的免疫抑制和改善癌症治疗结果提供了潜在的策略.
更多相关视频
08:02In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
2.6K
13:19Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
16.6K
相关概念视频
Mechanisms of Retrovirus-induced Cancers
5.1K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.1K
Replicative Cell Senescence
3.7K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.7K
Retroviruses
12.4K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.4K
Non-LTR Retrotransposons
11.6K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.6K
Rous Sarcoma Virus (RSV) and Cancer
5.1K
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
5.1K
The Extrinsic Apoptotic Pathway
6.5K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.5K
