Department of Microbiology, Immunology and Pathology, Des Moines University College of Osteopathic Medicine, West Des Moines, IA, 50266, USA.
Department of Psychology, Iowa State University, Ames, IA, 50011, USA.
Med Oncol. 2024 Nov 25;42(1):15. doi: 10.1007/s12032-024-02564-6.
Pancreatic ductal adenocarcinoma (PDAC) has proven to be a formidable cancer primarily due to its tumor microenvironment (TME). This highly desmoplastic, hypoxic, and pro-inflammatory environment has not only been shown to facilitate the growth and metastasis of PDAC but has also displayed powerful immunosuppressive capabilities. A critical cell involved in the development of the PDAC TME is the fibroblast, specifically the antigen-presenting cancer-associated fibroblast (apCAF). The pro-inflammatory environment of PDAC induces the proliferation of apCAFs, promoting immunosuppression through immune cell inactivation, immune response regulation, and expression of CD74. In conjunction with apCAFs and tumor cells, CD74 serves as a versatile promoter of PDAC by preventing tumor antigen-expression on tumor cells, upregulating the expression of immunosuppressive chemical mediators, and activating proliferative pathways to induce PDAC malignancy. This review will highlight critical mediators and pathways that promote the PDAC stroma and TME with its hypoxic and immunosuppressive properties. Further, we will highlight the nature of apCAFs and CD74, their specific roles in the PDAC TME, and their potential as targets for immunotherapy.
胰腺导管腺癌 (PDAC) 已被证明是一种难以攻克的癌症，主要是因为其肿瘤微环境 (TME)。这种高度纤维母细胞性、缺氧和促炎的环境不仅被证明有利于 PDAC 的生长和转移，而且还表现出强大的免疫抑制能力。在 PDAC TME 发育中涉及的关键细胞是成纤维细胞，特别是抗原呈递性癌相关成纤维细胞 (apCAF)。PDAC 的促炎环境诱导 apCAFs 的增殖，通过免疫细胞失活、免疫反应调节和 CD74 的表达促进免疫抑制。与 apCAFs 和肿瘤细胞一起，CD74 通过防止肿瘤细胞上的肿瘤抗原表达、上调免疫抑制化学介质的表达以及激活增殖途径来诱导 PDAC 恶性，是 PDAC 的多功能促进剂。这篇综述将重点介绍促进 PDAC 基质和具有缺氧和免疫抑制特性的 TME 的关键介质和途径。此外，我们将重点介绍 apCAFs 和 CD74 的性质、它们在 PDAC TME 中的特定作用以及它们作为免疫治疗靶点的潜力。
