瘤免疫微环境允许ING4缺乏乳腺癌的转移性进展
Emily Tsutsumi1,2, Anne M Macy3,4, Janine LoBello5
1Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, United States of America.
PloS one
|July 5, 2024
概括
乳腺癌中的ING4缺乏与免疫逃避和转移有关. 缺少ING4的瘤表现出抑制性免疫微环境,导致患者的存活率较低,特别是当大酶B (GZMB) 也很低时.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
背景情况:
- ING4瘤抑制剂缺乏与晚期癌症和患者存活率降低相关.
- ING4抑制NF-kB,一个关键的免疫反应媒介,表明在瘤免疫调节中的作用.
- 英格4缺乏对瘤免疫微环境的影响在很大程度上仍未得到研究.
研究的目的:
- 为了研究ING4缺陷乳腺瘤中的瘤免疫微环境.
- 分析与ING4状态和免疫标记器相关的免疫细胞透和患者存活率.
- 探索ING4损失对瘤进展和转移的功能影响.
主要方法:
- 246种原发性乳腺瘤 (97种ING4缺乏) 的组织微阵列被染色为免疫标记物 (CD68,CD4,CD8,PD-1).
- 一个具有CRISPR介导的Ing4删除的免疫能力的小鼠模型被用于通过流细胞计测量来评估瘤生长,转移和免疫标记.
- 分析了METABRIC基因表达数据集,以查找患者存活率,ING4表达和免疫标志物之间的相关性.
主要成果:
- 在人类乳腺瘤中,ING4缺乏与CD68,CD4,CD8或PD-1表达之间没有发现显著的关联.
- 被Ing4删除的小鼠瘤表现出类似的生长,但透率和转移率增加.
- 删除Ing4的瘤显示瘤相关的巨细胞增加和减少了大酶B阳性CD4+T细胞,表明免疫抑制的微环境.
- 低GZMB和ING4表达独立与基础乳腺癌的生存率差相关,联合低表达显示出最糟糕的结果.
结论:
- 缺少ING4的乳腺瘤的特点是免疫微环境促进免疫逃避和转移.
- 大酶B阳性CD4+T细胞的减少和与瘤相关的巨细胞的增加有助于减少瘤杀伤性环境.
- 联合低的ING4和GZMB表达意味着预后不佳,突出了针对这一轴的治疗潜力.
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