Bearing a dismal 5-year survival rate, pancreatic ductal adenocarcinoma (PDAC) is a challenging disease that features a unique fibroinflammatory tumor microenvironment. As major components of the PDAC tumor microenvironment, cancer-associated fibroblasts are still poorly understood and their contribution to the several hallmarks of PDAC, such as resistance to therapies, immunosuppression, and high incidence of metastasis, is likely underestimated. There have been encouraging advances in the understanding of these fascinating cells, but many controversies remain, leaving the field still actively exploring the full scope of their contributions in PDAC progression. Here we pose several important considerations regarding PDAC cancer-associated fibroblast functions. We posit that transcriptomic analyses be interpreted with caution, when aiming to uncover the functional contributions of these cells. Moreover, we propose that normalizing these functions, rather than eliminating them, will provide the opportunity to enhance therapeutic response. Finally, we propose that cancer-associated fibroblasts should not be studied in isolation, but in conjunction with its extracellular matrix, because their respective functions are coordinated and concordant.

中文翻译：

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重新思考癌症相关成纤维细胞在胰腺癌中的作用

胰腺导管腺癌 (PDAC) 的 5 年生存率很低，是一种具有挑战性的疾病，具有独特的纤维炎性肿瘤微环境。作为 PDAC 肿瘤微环境的主要组成部分，人们对癌症相关成纤维细胞仍知之甚少，并且它们对 PDAC 几个特征（如治疗耐药、免疫抑制和高转移发生率）的贡献可能被低估。对这些令人着迷的细胞的理解已经取得了令人鼓舞的进展，但仍然存在许多争议，使得该领域仍在积极探索它们在 PDAC 进展中的全部贡献。在这里，我们提出了关于 PDAC 癌症相关成纤维细胞功能的几个重要考虑因素。我们认为，在旨在揭示这些细胞的功能贡献时，应谨慎解释转录组分析。此外，我们建议使这些功能正常化，而不是消除它们，将提供增强治疗反应的机会。最后，我们建议癌症相关成纤维细胞不应单独研究，而应与其细胞外基质结合起来研究，因为它们各自的功能是协调一致的。