Table_5_Exploring aryl hydrocarbon receptor expression and distribution in the tumor microenvironment, with a focus on immune cells, in various solid cancer types.xlsx

IntroductionAryl hydrocarbon receptor (AhR) is a transcription factor that performs various functions upon ligand activation. Several studies have explored the role of AhR expression in tumor progression and immune surveillance. Nevertheless, investigations on the distribution of AhR expression, specifically in cancer or immune cells in the tumor microenvironment (TME), remain limited. Examining the AhR expression and distribution in the TME is crucial for gaining insights into the mechanism of action of AhR-targeting anticancer agents and their potential as biomarkers.MethodsHere, we used multiplexed immunohistochemistry (mIHC) and image cytometry to investigate the AhR expression and distribution in 513 patient samples, of which 292 are patients with one of five solid cancer types. Additionally, we analyzed the nuclear and cytosolic distribution of AhR expression.ResultsOur findings reveal that AhR expression was primarily localized in cancer cells, followed by stromal T cells and macrophages. Furthermore, we observed a positive correlation between the nuclear and cytosolic expression of AhR, indicating that the expression of AhR as a biomarker is independent of its localization. Interestingly, the expression patterns of AhR were categorized into three clusters based on the cancer type, with high AhR expression levels being found in regulatory T cells (Tregs) in non-small cell lung cancer (NSCLC).DiscussionThese findings are anticipated to serve as pivotal evidence for the design of clinical trials and the analysis of the anticancer mechanisms of AhR-targeting therapies.

引言（Introduction）
芳烃受体（Aryl hydrocarbon receptor, AhR）作为一种转录因子，在配体激活后执行多种功能。众多研究已探讨AhR表达在肿瘤进展和免疫监视中的作用。然而，关于AhR表达分布的研究，特别是在肿瘤微环境（TME）中的肿瘤或免疫细胞中的分布，尚显不足。考察TME中AhR的表达与分布，对于深入理解AhR靶向抗癌药物的药理作用机制及其作为生物标志物的潜力至关重要。
方法（Methods）
本研究采用多重免疫组化（multiplexed immunohistochemistry, mIHC）和图像细胞计数技术，对513例患者的样本进行AhR表达和分布的研究，其中292例患有五种实体瘤中的一种。此外，我们还分析了AhR在细胞核和细胞质中的分布。
结果（Results）
我们的研究发现，AhR表达主要定位于癌细胞，其次为间质T细胞和巨噬细胞。此外，我们还观察到AhR的核质表达之间存在正相关，表明AhR作为生物标志物的表达与其定位无关。有趣的是，根据癌症类型，AhR的表达模式被分为三个簇，在非小细胞肺癌（NSCLC）中，调节性T细胞（Tregs）表现出高AhR表达水平。
讨论（Discussion）
这些发现有望为临床试验的设计和AhR靶向治疗抗癌机制的解析提供关键证据。