Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, University of Dresden, Dresden, Germany.
German Cancer Consortium (DKTK), Partner Site Dresden; and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Oncogene. 2020 Apr;39(15):3102-3113. doi: 10.1038/s41388-020-1186-7. Epub 2020 Feb 13.
Pancreatic ductal adenocarcinoma (PDAC) responds poorly to checkpoint blockade, such as anti-CTLA-4 and anti-PD-1. Galectin-9, a β-galactoside-binding lectin, promotes immune suppression through T-cell inhibition, and programming of tolerogenic macrophages. Of all cancers tested, PDAC showed the highest expression of LGALS9 (galectin-9) mRNA. We analyzed formalin-fixed and paraffin-embedded specimens from 83 patients with PDAC stained for galectin-9. Using flow cytometry, we determined galectin-9 expression on immune cells from tumor and matched blood samples from 12 patients with resectable PDAC. Furthermore, we analyzed galectin-9 serum levels by enzyme-linked immunosorbent assay using serum samples from 70 patients with PDAC, from 36 individuals with benign pancreatic disease, and from 28 healthy controls. Galectin-9 was highly expressed in human PDAC compared with normal pancreas and present on both tumor and immune cells. Tumor-infiltrating immune cells, especially CD3 T cells, showed upregulation of galectin-9 compared with immune cells from matched blood. Blood γδ T cells from PDAC patients had higher galectin-9 expression than γδ T cells from healthy individuals. Galectin-9 polarized macrophages toward a protumoral M2 phenotype leading to suppressed T-cell cytokine secretion. Furthermore, serum concentration of galectin-9 was able to discriminate PDAC from benign pancreatic disease and healthy individuals, and was prognostic for stage IV patients. Galectin-9 is a new biomarker for the detection of PDAC.
胰腺导管腺癌 (PDAC) 对检查点阻断反应不佳，例如抗 CTLA-4 和抗 PD-1。半乳糖凝集素-9（Galectin-9）是一种 β-半乳糖苷结合凝集素，通过 T 细胞抑制和耐受性巨噬细胞的编程促进免疫抑制。在所有测试的癌症中，PDAC 表现出最高的 LGALS9（半乳糖凝集素-9）mRNA 表达。我们分析了 83 例 PDAC 患者的福尔马林固定石蜡包埋标本，这些患者的标本均对半乳糖凝集素-9 进行了染色。通过流式细胞术，我们确定了 12 例可切除 PDAC 患者肿瘤和匹配血液样本中免疫细胞的半乳糖凝集素-9 表达。此外，我们使用来自 70 例 PDAC 患者、36 例良性胰腺疾病患者和 28 例健康对照者的血清样本通过酶联免疫吸附试验分析了半乳糖凝集素-9 的血清水平。与正常胰腺相比，人类 PDAC 中半乳糖凝集素-9 表达水平较高，并且存在于肿瘤和免疫细胞上。与匹配血液中的免疫细胞相比，肿瘤浸润免疫细胞，特别是 CD3 T 细胞，半乳糖凝集素-9 表达上调。与健康个体相比，PDAC 患者的血液 γδ T 细胞表达更高的半乳糖凝集素-9。半乳糖凝集素-9 将巨噬细胞极化到促肿瘤 M2 表型，导致 T 细胞细胞因子分泌受到抑制。此外，半乳糖凝集素-9 的血清浓度能够区分 PDAC 与良性胰腺疾病和健康个体，并且对 IV 期患者具有预后价值。半乳糖凝集素-9 是检测 PDAC 的新生物标志物。
