相关实验视频

Updated: May 5, 2026

The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers

The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers

Published on: January 22, 2013

低pH,高风险:一个叙述性回顾探索酸感应GPR65途径作为细胞癌的新方法

Michael Grant^1,2, Barbara Cipriani³, Alastair Corbin³

¹St Bartholomew's Hospital, London EC1A 7BE, UK.

|December 11, 2025

概括

用GPR65抑制剂向细胞癌 (RCC) 中的酸性瘤可以克服免疫逃避和抵抗免疫检查点抑制剂 (ICI) 等疗法. 这种方法旨在恢复抗瘤免疫力,以改善患者的治疗结果.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
瘤微环境瘤微环境

背景情况:

细胞癌 (RCC) 是一种异质性癌症,对当前的免疫检查点抑制剂 (ICI) 等治疗方法的持续反应有限.
在RCC中,酸性瘤微环境 (TME) 通过损害免疫细胞功能和上调免疫抑制机制,促进免疫逃避和治疗耐药性.
在TME中的酸与增强的葡萄糖分解,乳酸积累和过度表达pH调节剂,如碳酸无酶9 (CA9) 有关.

研究的目的:

研究酸性TME和质子感应G蛋白合受体 (GPCRs),特别是GPR65在RCC进展和治疗耐药性中的作用.
评估针对GPR65作为一种新的治疗策略,以克服免疫逃避并提高RCC中的ICI疗效的潜力.

主要方法:

对临床前和临床证据的审查,这些证据涉及RCC中的TME酸化和GPR65.
分析GPR65对抗机制,包括逆转免疫抑制和增强抗原处理.
在RCC模型中检查GPR65抑制剂的作用,包括与抗PD-1疗法的协同作用.

主要成果:

酸性TME会损害细胞毒性T细胞和NK细胞的活动,促进免疫抑制的TAMs,并提高免疫检查点的调节,从而促进ICI耐药性.
GPR65对抗剂通过逆转化驱动的免疫抑制来恢复抗瘤免疫力的临床前有效性.
在RCC模型中,GPR65抑制剂降低了IL-10,诱导了免疫蛋白酶激活,并与抗PD-1疗法协同作用.

结论:

针对酸感应通路,特别是GPR65,是重塑TME并克服RCC中的ICI抵抗的新策略.
抑制GPR65有望提高现有的免疫疗法在RCC管理中的疗效.
第一类GPR65抑制剂PTT-4256正在临床研究中,突出显示了这种方法的翻译潜力.

关键词:

在 GPR65 中使用.碳酸无水酶IX的使用方法免疫检查点抑制剂免疫检查点抑制剂免疫疗法免疫疗法细胞癌瘤是细胞癌.治疗耐药性的治疗.瘤酸性酸性疾病的发生.瘤微环境是一个微环境.

更多相关视频

Establishment of an Extracellular Acidic pH Culture System

Establishment of an Extracellular Acidic pH Culture System

Published on: November 19, 2017

Microfluidic Co-culture of Renal Healthy and Tumor Epithelium to Model Kidney Cancer Progression

Microfluidic Co-culture of Renal Healthy and Tumor Epithelium to Model Kidney Cancer Progression

Published on: January 31, 2025

相关概念视频

Transducer Mechanism: Enzyme-Linked Receptors

Transducer Mechanism: Enzyme-Linked Receptors

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:

Renal Regulation of Acid-Base Balance

Renal Regulation of Acid-Base Balance

Metabolic reactions in the body produce nonvolatile acids, such as sulfuric acid, which generate an acid load of approximately 1 mEq of H+ per kilogram of body weight daily. Excreting H+ in the urine is essential to balance this acid load.
In the kidneys, cells within the proximal convoluted tubules (PCT) and the collecting ducts secrete hydrogen ions (H+) into the tubular fluid. Specifically, in the PCT, Na+/H+ antiporters secrete H+ while reabsorbing Na+.
However, the intercalated cells in...