瘤干扰素信号调节对免疫检查点阻断的多基因抵抗程序
Joseph L Benci1, Bihui Xu1, Yu Qiu1
1Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell
|December 3, 2016
概括
长时间的干扰素信号驱动抗癌免疫疗法,如PD1阻断. 抑制这种信号可以恢复抗瘤免疫力,并改善对检查点抑制剂的反应.
科学领域:
- 免疫学
- 癌症学
- 分子生物学
背景情况:
- 针对PD1通路的免疫检查点阻塞 (ICB) 疗法显示出显著的抗瘤功效.
- 然而,对ICB的耐药性是一个常见的临床挑战,限制了治疗的成功.
- 了解抵抗机制对于改善癌症免疫治疗结果至关重要.
研究的目的:
- 调查长期干扰素信号传递对ICB和组合疗法的中介性抵抗的作用.
- 为了确定干扰素驱动的分子路径.
- 探索克服这种抵抗的治疗策略.
主要方法:
- 对瘤样本和T细胞群的分析.
- 对干扰素信号通路的遗传和药理操作.
- 评估T细胞功能和瘤对免疫治疗的反应.
主要成果:
- 长时间的I型和II型干扰素信号促进了PDL1依赖的和独立的对ICB和组合疗法的耐药性.
- 干扰素信号诱导与STAT1相关的表观基因变化,并上调抑制性受体连接体.
- 抑制干扰素信号恢复T细胞功能,使得耐药瘤对ICB单一治疗敏感.
- 干扰素驱动的耐药性生物标志物与抗PD1治疗后的临床进展相关.
结论:
- 瘤干扰素信号传递是适应性抗癌免疫疗法的关键驱动因素.
- 向干扰素反应途径可以克服耐药性并增强抗瘤免疫力.
- 抑制干扰素信号可能会绕过复杂的组合免疫疗法方案的需要.
相关概念视频
Tumor Immunotherapy
2.1K
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.
2.1K
mTOR Signaling and Cancer Progression
5.0K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
5.0K
Interactions Between Signaling Pathways
7.7K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.7K
Tumor Progression
7.7K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.7K
Cancer-Critical Genes II: Tumor Suppressor Genes
10.0K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.0K
The Tumor Microenvironment
8.0K
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...
8.0K


