Disease-induced immunomodulation at biomaterial scaffolds detects early pancreatic cancer in a spontaneous model. (February 2021)

• Record Type: Journal Article
• Authors: Bushnell, Grace G.; Orbach, Sophia M.; Ma, Jeffrey A.; Crawford, Howard C.; Wicha, Max S.; Jeruss, Jacqueline S.; Shea, Lonnie D.
• Is Part Of: Biomaterials. Volume 269(2021)
• Publication Date: 2021-02
• Subjects: Metastasis -- Biomaterials -- Pancreatic cancer -- Immunomodulation; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2020.120632
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Pancreatic cancer has the worst prognosis of all cancers due to disease aggressiveness and paucity of early detection platforms. We developed biomaterial scaffolds that recruit metastatic tumor cells and reflect the immune dysregulation of native metastatic sites. While this platform has shown promise in orthotopic breast cancer models, its potential in other models is untested. Herein, we demonstrate that scaffolds recruit disseminated pancreatic cells in the KPCY model of spontaneous pancreatic cancer prior to adenocarcinoma formation (3-fold increase in scaffold YFP + cells). Furthermore, immune cells at the scaffolds differentiate early- and late-stage disease with greater accuracy (0.83) than the natural metastatic site (liver, 0.50). Early disease was identified by an approximately 2-fold increase in monocytes. Late-stage disease was marked by a 1.5-2-fold increase in T cells and natural killer cells. The differential immune response indicated that the scaffolds could distinguish spontaneous pancreatic cancer from spontaneous breast cancer. Collectively, our findings demonstrate the utility of scaffolds to reflect immunomodulation in two spontaneous models of tumorigenesis, and their particular utility for identifying early disease stages in the aggressive KPCY pancreatic cancer model. Such scaffolds may serve as a platform for early detection of pancreatic cancer to improve treatment and prognosis. Graphical abstract: Image 1