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NOS2和COX2提供了关键的空间目标,以确定ER-乳腺癌的结果

Lisa A Ridnour¹, William F Heinz², Robert Ys Cheng¹

¹Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD.

bioRxiv : the preprint server for biology

|January 8, 2024

概括

瘤诱导氧化合成酶 (NOS2) 和循环氧化酶 (COX2) 在雌激素受体阴性乳腺癌中的表达与明显的CD8+T细胞表型和患者存活率相关. 高NOS2/COX2与侵袭性瘤微环境和不良结果有关.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

雌激素受体阴性 (ER-) 乳腺癌在有限的治疗条件下具有侵略性.
诱导性氧化合成酶 (NOS2) 和循环氧化酶 (COX2) 的上调预测ER-乳腺癌的结果不佳.
这些酶影响癌症干细胞,转移和免疫抑制.

研究的目的:

研究瘤NOS2/COX2表达和ER乳腺癌中瘤免疫微环境之间的关系.
识别与患者存活相关的不同的CD8+T细胞表型.
探索免疫标记物,癌症干细胞标记物和患者结果之间的空间相关性.

主要方法:

对21个ER-乳腺瘤进行多重光成像.
与NOS2和COX2表达相关的CD8+T细胞表型的分析.
在验证队列中的基因表达分析.
无监督的非线性维度缩小 (UMAP) 用于空间分析.
癌症干细胞标记物的空间分析 (CD44v6,EpCAM).

主要成果:

高NOS2/COX2表达与5年生存率差相关.
显而易见的CD8+T细胞表型与生存相关:CD8+NOS2-COX2-在活着的患者中 (低NOS2/COX2),CD8+NOS2+COX2+或CD8-NOS2-COX2+在已故患者中 (高NOS2/COX2).
空间分析显示了EpCAM和CD8+NOS2+COX2+表型,以及CD44v6和COX2在已故患者免疫沙漠区域之间的相关性.
在CD8-NOS2+COX2+区域中发现了迁移的瘤细胞,这表明转移性热点.

结论:

NOS2/COX2和CD8+T细胞的空间定位塑造了ER乳腺癌中的瘤免疫微环境.
特定的空间模式与侵略性的瘤表型和不良的临床结果有关.
这种空间分析方法可以识别攻击性瘤,并告知使用NOS2/COX2抑制剂或免疫调节剂的潜在治疗策略.

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