Clinic for Gastroenterology, Endocrinology, Metabolism and Infectiology, Philipps-University Marburg, Marburg, Germany.
Institute for Immunology, Philipps-University Marburg, Marburg, Germany.
Cancer Med. 2023 Apr;12(7):8542-8556. doi: 10.1002/cam4.5606. Epub 2023 Jan 5.
Toll-like receptors (TLRs) are gaining attention for their potential to influence tumor biology both on the level of the tumor cells as well as on the level of the surrounding inflammatory stroma. Previous studies resulted in partly conflicting data on the expression of TLR7 in healthy and neoplastic pancreatic tissues as well as its role in pancreatic tumor biology.
We used qRT-PCR and immunohistochemistry to asses TLR7 expression in primary patient material and cell lines. Cell viability was analyzed by MTT assay upon incubation with TLR7 agonist/antagonist. Mouse models were used to investigate the role of TLR7 in vivo.
TLR7 is overexpressed in more than 50% of primary human pancreatic ductal adenocarcinoma (PDAC). High TLR7 expression was associated with shorter patient survival, and TLR7 inhibition in cell lines reduced viability in a dose-dependent manner. In contrast, global TLR7 deficiency did not alter survival or overall histopathological tumor features in genetic mouse models of PDAC.
TLR7 may have opposing functions in tumor versus stroma cells. Further work is required to more precisely dissect the roles of TLR7 and its ligands in different populations of epithelial and stromal cells and to understand their relative contributions to tumor progression.
Toll 样受体 (TLRs) 因其有可能影响肿瘤细胞和周围炎症基质的肿瘤生物学而受到关注。先前的研究结果表明 TLR7 在健康和肿瘤胰腺组织中的表达及其在胰腺肿瘤生物学中的作用存在部分矛盾的数据。
我们使用 qRT-PCR 和免疫组织化学分析来评估原发性患者标本和细胞系中 TLR7 的表达。用 TLR7 激动剂/拮抗剂孵育后通过 MTT 分析测定细胞活力。使用小鼠模型来研究 TLR7 在体内的作用。
TLR7 在超过 50%的原发性人胰腺导管腺癌 (PDAC) 中过度表达。高 TLR7 表达与患者生存时间缩短相关，细胞系中 TLR7 抑制呈剂量依赖性降低细胞活力。相比之下，在 PDAC 的遗传小鼠模型中，全身性 TLR7 缺乏并未改变生存或总体组织病理学肿瘤特征。
TLR7 在肿瘤细胞与基质细胞中的作用可能相反。需要进一步的工作来更精确地剖析 TLR7 及其配体在不同上皮细胞和基质细胞群体中的作用，并了解它们对肿瘤进展的相对贡献。
