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阻止CCR1巨细胞克服了黑色素瘤中免疫检查点抑制剂的抵抗力

Xinyu Su^1,2, Rong Huang¹, Donglin Kang³

¹Department of the Comprehensive Cancer Center, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China.

Cell communication and signaling : CCS

|November 4, 2025

概括

化基因受体CCR1通过连接CCR1+巨细胞和CD8+耗尽的T细胞来塑造瘤微环境. 准这一轴可增强黑色素瘤中抗PD-1治疗反应.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
癌症研究癌症研究

背景情况:

化学因子和受体对于瘤微环境 (TME) 调节和免疫反应至关重要.
在TME中化学激素信号传递的机制尚未完全理解.
了解这些相互作用是改善癌症免疫疗法的关键.

研究的目的:

研究CCR1+巨细胞和CD8+耗尽的T (Tex) 细胞在黑色素瘤中的作用.
探索这些细胞,化学信号传递和免疫检查点阻塞 (ICB) 治疗反应之间的关系.
确定克服ICB耐药性的治疗策略.

主要方法:

利用多种omics方法来分析细胞群和信号通路.
在黑色素瘤模型中研究了CCR1+巨细胞和ICB结果之间的关联.
在小鼠模型中评估了使用CCR1抗剂和抗PD-1抗体的联合治疗.
在人类黑色素瘤和小鼠模型中分析了CCR1+巨细胞和CD8+Tex细胞的共同定位.

主要成果:

在黑色素瘤中,CCR1+巨细胞与ICB治疗反应显著相关.
组合疗法 (CCR1抗剂+抗PD-1) 通过消耗CD8+Tex细胞来降低瘤负担.
在人类黑色素瘤中,CCR1+巨细胞和CD8+Tex细胞形成了一个与人类黑色素瘤共同局部化的利基,并与小鼠的ICB反应相关联.
确定了CCR1-CCL3轴作为这个利基形成的关键调解器.

结论:

在黑色素瘤中,CCR1+巨细胞和CD8+Tex细胞之间的空间关系对于ICB治疗疗效至关重要.
针对CCR1-CCL3轴提供了一个潜在的战略来克服ICB阻力.
这项研究为改善黑色素瘤治疗结果提供了一种新的治疗方法.

关键词:

CCR1 CCR1 的意思是什么?CD8+ T 细胞的细胞.免疫治疗是一种免疫疗法.巨细胞是一个巨细胞.瘤微环境是一个微环境.

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