Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal; Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, 4200-135 Porto, Portugal; Department of Biological Sciences, Faculty of Pharmacy of the University of Porto (FFUP), Porto, Portugal.
Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal; Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, 4200-135 Porto, Portugal.
Trends Mol Med. 2023 Jun;29(6):439-453. doi: 10.1016/j.molmed.2023.03.002. Epub 2023 Apr 24.
Pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs) are highly abundant cells in the pancreatic tumor microenvironment (TME) that modulate desmoplasia. The formation of a dense stroma leads to immunosuppression and therapy resistance that are major causes of treatment failure in pancreatic ductal adenocarcinoma (PDAC). Recent evidence suggests that several subpopulations of CAFs in the TME can interconvert, explaining the dual roles (antitumorigenic and protumorigenic) of CAFs in PDAC and the contradictory results of CAF-targeted therapies in clinical trials. This highlights the need to clarify CAF heterogeneity and their interactions with PDAC cells. This review focuses on the communication between activated PSCs/CAFs and PDAC cells, as well as on the mechanisms underlying this crosstalk. CAF-focused therapies and emerging biomarkers are also outlined.
胰腺星状细胞（PSCs）和癌相关成纤维细胞（CAFs）是胰腺肿瘤微环境（TME）中高度丰富的细胞，可调节细胞外基质的形成。致密基质的形成导致免疫抑制和治疗耐药，这是胰腺导管腺癌（PDAC）治疗失败的主要原因。最近的证据表明，TME 中的几种 CAF 亚群可以相互转化，这解释了 CAF 在 PDAC 中的双重作用（抗肿瘤和促肿瘤）以及临床试验中 CAF 靶向治疗的矛盾结果。这凸显了需要阐明 CAF 异质性及其与 PDAC 细胞的相互作用。本综述重点关注活化的 PSCs/CAFs 与 PDAC 细胞之间的通讯，以及这种串扰的潜在机制。还概述了针对 CAF 的治疗方法和新兴的生物标志物。
