Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), has an immune suppressive environment that allows tumour cells to evade the immune system. The aryl-hydrocarbon receptor (AHR) is a transcription factor that can be activated by certain exo/endo ligands, including kynurenine (KYN) and other tryptophan metabolites. Once activated, AHR regulates the expression of various genes involved in immune responses and inflammation. Previous studies have shown that AHR activation in PDAC can have both pro-tumorigenic and anti-tumorigenic effects, depending on the context. It can promote tumour growth and immune evasion by suppressing anti-tumour immune responses or induce anti-tumour effects by enhancing immune cell function. In this study involving 30 PDAC patients and 30 healthy individuals, peripheral blood samples were analysed. PDAC patients were categorized into Low (12 patients) and High/Medium (18 patients)AHRgroups based on gene expression in peripheral blood mononuclear cells (PBMCs). The LowAHRgroup showed distinct immune characteristics, including increased levels of immune-suppressive proteins such as PDL1, as well as alterations in lymphocyte and monocyte subtypes. Functional assays demonstrated changes in phagocytosis, nitric oxide production, and the expression of cytokinesIL-1,IL-6, andIL-10. These findings indicate thatAHR’s expression level has a crucial role in immune dysregulation in PDAC and could be a potential target for early diagnostics and personalised therapeutics.
胰腺癌，特别是胰腺导管腺癌（PDAC），具有免疫抑制微环境，使肿瘤细胞能够逃避免疫系统的攻击。芳香烃受体（AHR）是一种转录因子，可被某些外源性/内源性配体激活，包括犬尿氨酸（KYN）和其他色氨酸代谢物。一旦激活，AHR会调控多种参与免疫反应和炎症的基因表达。先前研究表明，PDAC中AHR的激活可能具有促肿瘤和抗肿瘤双重效应，具体取决于微环境。它可通过抑制抗肿瘤免疫反应促进肿瘤生长和免疫逃逸，或通过增强免疫细胞功能诱导抗肿瘤效应。本研究纳入30例PDAC患者和30名健康个体，对其外周血样本进行分析。根据外周血单个核细胞（PBMCs）的基因表达，将PDAC患者分为低AHR组（12例）和高/中AHR组（18例）。低AHR组表现出独特的免疫特征，包括PD-L1等免疫抑制蛋白水平升高，以及淋巴细胞和单核细胞亚型的改变。功能实验显示，该组在吞噬作用、一氧化氮产生以及细胞因子IL-1、IL-6和IL-10的表达方面均发生变化。这些发现表明，AHR的表达水平在PDAC免疫失调中起关键作用，可能成为早期诊断和个体化治疗的潜在靶点。
肿瘤(癌症)患者之家