Shinkawa Tomohiko, Ohuchida Kenoki, Nakamura Masafumi
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 819-0395, Japan.
Cancers (Basel). 2022 Aug 18;14(16):3994. doi: 10.3390/cancers14163994.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival rate of 9%. Cancer-associated fibroblasts (CAFs) have historically been considered tumor-promoting. However, multiple studies reporting that suppression of CAFs in PDAC mouse models resulted in more aggressive tumors and worse prognosis have suggested the existence of a tumor-suppressive population within CAFs, leading to further research on heterogeneity within CAFs. In recent years, the benefits of cancer immunotherapy have been reported in various carcinomas. Unfortunately, the efficacy of immunotherapies in PDAC has been limited, and the CAF-driven cancer immunosuppressive microenvironment has been suggested as the cause. Thus, clarification of heterogeneity within the tumor microenvironment, including CAFs and tumor immunity, is urgently needed to establish effective therapeutic strategies for PDAC. In this review, we report the latest findings on the heterogeneity of CAFs and the functions of each major CAF subtype, which have been revealed by single-cell RNA sequencing in recent years. We also describe reports of tumor-suppressive CAF subtypes and the existence of CAFs that maintain a differentiated PDAC phenotype and review the potential for targeted therapy.
胰腺导管腺癌（PDAC）是最致命的癌症之一，5年生存率为9%。癌症相关成纤维细胞（CAFs）历来被认为具有促肿瘤作用。然而，多项研究报告称，在PDAC小鼠模型中抑制CAFs会导致肿瘤更具侵袭性且预后更差，这表明CAFs中存在具有肿瘤抑制作用的亚群，从而引发了对CAFs异质性的进一步研究。近年来，癌症免疫疗法在各种癌症中均有疗效报道。遗憾的是，免疫疗法在PDAC中的疗效有限，有人认为CAF驱动的癌症免疫抑制微环境是其原因。因此，迫切需要阐明肿瘤微环境中的异质性，包括CAFs和肿瘤免疫，以建立有效的PDAC治疗策略。在这篇综述中，我们报告了近年来通过单细胞RNA测序揭示的CAFs异质性及各主要CAF亚型功能的最新研究结果。我们还描述了具有肿瘤抑制作用的CAF亚型的报道以及维持分化型PDAC表型的CAFs的存在，并综述了靶向治疗的潜力。
