Abstract PO025: GM-CSF neutralization enhances the efficacy of chemotherapy in an orthotopic murine model of cholangiocarcinoma

• Published in: Clinical cancer research 2022-09, Vol.28 (17_Supplement), p.PO025-PO025
• Main Authors: Dave, Yatee A, Burchard, Paul R, Ullman, Nicholas A, Georger, Mary, Ruffolo, Luis I, Belt, Brian A, Linehan, David C
• Format: Article
• Language: English
• ISSN: 1557-3265; 1557-3265
• DOI: 10.1158/1557-3265.LIVERCA22-PO025

Introduction: With current effective treatments in cholangiocarcinoma (CCA) lacking, we expounded on our prior work highlighting the critical role of the granulocyte-macrophage-colony stimulating factor ligand/receptor (GM-CSF/GM-CSFRα) signaling pathway by evaluating GM-CSF neutralization combined with first-line chemotherapy in a novel murine model of CCA. Methods: Resected CCA specimens were used to construct a human tissue macro-array. Immunohistochemistry (IHC) staining for GM-CSFRα and digital quantification of staining intensity was performed. A novel syngeneic CCA cell line derived from spontaneous murine CCA from LSL-KrasG12D; Tp53Flox/Flox −; Alb-Cre (KPPC) mice was surgically injected into the left hepatic lobes of C57BL/6J mice. Disease onset and extent of progression was monitored over time using ultrasonography (US) in groups of mice enrolled into treatment with vehicle, gemcitabine, anti-GM-CSF, and gemcitabine plus anti-GM-CSF. Mice were sacrificed at predetermined endpoints for flow cytometry analysis. Results: IHC analysis and digital quantification of resected human tumors demonstrated that CCA expresses significantly higher levels of GM-CSFRα (p