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针对树突细胞功能障碍,绕过头癌中抗PD1抵抗的方法

Shin Saito¹, Michihisa Kono¹, Hoang C B Nguyen²

¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Clinical cancer research : an official journal of the American Association for Cancer Research

|February 19, 2024

概括

1型常规树突细胞 (cDC1) 功能障碍有助于在头部和部状细胞癌 (HNSCC) 中抗PD1 (aPD1) 耐药性. 增强cDC1透和功能,可能通过CCL5,可以恢复aPD1的敏感性并改善瘤控制.

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:

新辅助性抗PD1 (aPD1) 疗法在头部和部状细胞癌 (HNSCC) 中表现有前途.
对aPD1疗法的耐药性机制需要进一步调查,以改善患者的治疗结果.
了解免疫细胞在HNSCC治疗反应中的作用至关重要.

研究的目的:

研究HNSCC. aPD1抗性的机制.
为了确定免疫细胞群对HNSCC.aPD1反应至关重要.
探索克服HNSCC中的aPD1抵抗的策略.

主要方法:

综合分析合成性小鼠口腔癌 (MOC) 模型和HNSCC患者RNA测序数据.
在瘤排水淋巴结 (DLN) 中对抗原特异性T细胞原始化的评估.
在aPD1-耐药模型中评估1型常规树突细胞 (cDC1) 功能和瘤微环境.

主要成果:

在小鼠模型中,aPD1耐药性与cDC1功能障碍和T细胞反应受损有关.
在小鼠模型和HNSCC患者中,减少cDC1透与aPD1抵抗相关.
内cDC1疫苗接种和CCL5表达通过增强T细胞透和反应恢复了aPD1的敏感性.

结论:

瘤透cDC1在HNSCC对aPD1治疗的反应中起着至关重要的作用.
增强cDC1透和功能的策略可以克服HNSCC中的aPD1抵抗.
CCL5成为一个潜在的治疗点,以提高aPD1在HNSCC中的疗效.

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