与受体相互作用的蛋白激酶2是胰腺癌的免疫治疗点
Wenhua Sang1, Yiduo Zhou2, Haiyan Chen3
1Department of Colorectal Surgery & Oncology of the Second Affiliated Hospital, and Department of Pathology & Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
Cancer discovery
|October 12, 2023
概括
在胰腺癌 (PDAC) 中准受体相互作用蛋白激酶2 (RIPK2) 克服了免疫逃避. 抑制RIPK2增强了抗PD-1免疫疗法,在PDAC模型中改善了生存率和瘤回归.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 胰腺管腺癌 (PDAC) 是一种致命的癌症,治疗选择有限.
- 人们对PDAC中的瘤免疫微环境 (TME) 的了解很少,导致治疗耐药性.
- 现有的疗法,包括免疫检查点封锁,对PDAC基本上无效.
研究的目的:
- 在PDAC瘤免疫微环境中识别新的治疗点.
- 研究受体相互作用蛋白激酶2 (RIPK2) 在PDAC免疫逃避中的作用.
- 评估向RIPK2与抗PD-1免疫疗法结合的疗效.
主要方法:
- 在正方形PDAC模型中利用基因组和膜组聚焦的CRISPR查.
- 进行了RIPK2.2的遗传和药理向.
- 进行了机制研究,以阐明RIPK2在TME调节和抗原呈现中的作用.
主要成果:
- 受体相互作用蛋白激酶2 (RIPK2) 被确定为PDAC中免疫逃避的关键驱动因素.
- 准RIPK2使PDAC对抗PD-1免疫疗法的敏感,导致显著的生存益处和瘤回归.
- 通过抑制NBR1-介导的自-溶酶体降解,RIPK2抑制破坏了脱塑性TME,并恢复了MHC I类表面水平.
结论:
- 在PDAC中,RIPK2是免疫逃避的关键调节者.
- 对RIPK2抑制和抗PD-1免疫疗法的联合治疗显示出治疗PDAC的前景.
- 向RIPK2提供了一种新的策略,以克服胰腺癌中免疫治疗的耐药性.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
mTOR Signaling and Cancer Progression
3.8K
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...
3.8K
The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K
Tumor Immunotherapy
539
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.
539
Transducer Mechanism: Enzyme-Linked Receptors
2.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.5K
Interactions Between Signaling Pathways
6.3K
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...
6.3K


