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瘤微环境控制了头支状细胞癌免疫疗法的预后格局:以计算模型为指导的分析

Priyan Bhattacharya¹, Alban Linnenbach², Andrew P South³

¹Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.

PLoS computational biology

|June 3, 2025

概括

这项研究模拟了头部和部状细胞癌瘤微环境 (TME),以了解免疫检查点抑制 (ICI) 抵抗. 独特的TME亚型影响ICI反应,预测特定的疗法和生物标志物可以改善结果.

科学领域:

计算生物学是一种计算生物学.
免疫学免疫学免疫学
在瘤学瘤学.

背景情况:

免疫检查点抑制 (ICI) 对于治疗头部和部状细胞癌 (HNSCC) 至关重要.
瘤微环境 (TME) 相互作用显著影响HNSCC对ICI的反应.
了解各种TME亚型及其对ICI疗效的影响至关重要.

研究的目的:

开发HNSCC TME的细胞分子模型.
识别不同的TME亚型及其与ICI响应的相关性.
预测ICI耐药HNSCC的新型治疗策略和生物标志物.

主要方法:

开发了一个HNSCC TME的细胞分子模型.
模拟多种细胞类型,状态和分子信号之间的相互作用.
分析参数空间以识别不同的TME亚型.

主要成果:

确定了五种临床观察到的HNSCC TME亚型.
预测与癌症相关的纤维细胞阻碍CD8+T细胞透,恶化ICI反应.
在免疫沙漠情景中展示了IL-2 + ICI联合治疗的潜在好处.
在纤维主导的场景中,确定了骨质疏松素 (OPN) 和白血病抑制因子 (LIF) 淘汰作为有益的.
预测IL-8和乳酸作为ICI耐药性的生物标志物.

结论:

开发的模型为理解HNSCC中TME介导的ICI电阻提供了一个定量框架.
特定的TME亚型需要量身定制的治疗方法来改善ICI结果.
鉴定了介质素-8 (IL-8) 和乳酸盐作为预测HNSCC中的ICI耐药性的潜在生物标志物.

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