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向氧化酸化以提高免疫组合治疗在细胞癌中疗效

Jihua Tian^1,2, Jing Luo³, Xing Zeng¹

¹Department of Urology, Tongji Hospital Affiliated Tongji Medical College of Huazhong University of Science and Technology (HUST), Wuhan, China.

Journal for immunotherapy of cancer

|February 14, 2024

概括

高氧化酸化 (OXPHOS) 水平预测在转移性细胞癌 (RCC) 中对免疫检查点抑制剂 (ICI) 的耐药性. 向OXPHOS可能通过增强瘤微环境中的T细胞功能来改善免疫治疗反应.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
代谢过程中的代谢.

背景情况:

免疫检查点抑制剂 (ICI) 是转移性细胞癌 (RCC) 的标准治疗方法.
大多数患者对ICI产生耐药性,需要新的治疗策略.
氧化酸化 (OXPHOS) 尚未被广泛研究为克服ICI耐药性的目标.

研究的目的:

调查RCC中OXPHOS和ICI电阻之间的关系.
探索OXPHOS作为一种潜在的目标,以提高RCC的免疫疗法疗效.

主要方法:

对RNA测序和来自多个RCC临床试验的临床数据的系统分析.
对通吉医院RCC患者临床病理学数据的分析.
使用Ndufb8-knockdown Renca细胞系进行体内研究,以评估OXPHOS在RCC免疫治疗中的作用.

主要成果:

高水平的OXPHOS被确定为RCC中ICI耐药性的风险因素,受VHL和HIF-1α状态的影响.
在Renca细胞中,Ndufb8的敲击减缓了体内瘤生长,并改善了与抗PD-L1疗法治疗的小鼠的生存率.
减少瘤中的OXPHOS与增加的CD8+T细胞透,减少缺氧和增强的抗瘤免疫反应 (降低PD-1/TIM-3表达,增加IFN-γ分泌) 相关联.

结论:

在RCC中,OXPHOS是免疫治疗反应的可靠预测剂,特别是在转移性病变中.
RCC细胞利用氧化代谢来创建低氧瘤微环境,抑制T细胞功能并导致ICI耐药性.
针对OXPHOS可能是一个可行的策略,以克服RCC中的ICI阻力.

关键词:

免疫治疗是一种免疫疗法.代谢网络和途径细胞癌是细胞癌.

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