Xi He
Pronouns: She, Her, Hers
Research Mentor(s): Yaqing Zhang
Co-Presenter:
Research Mentor School/College/Department: Surgery / Medicine
Presentation Date: April 20
Presentation Type: Oral5
Session: Session 6 – 4:40pm – 5:30 pm
Room: Breakout room 6
Authors:
Presenter: 3
Abstract
C-C chemokine receptor-1 (CCR1) is highly expression in tumor-associated macrophages and may play an important role in the infiltration of myeloid cells in pancreatic cancer, based on our previous study. To investigate its role in tumor-associated macrophages and the immunosuppressive tumor microenvironment, we used three approaches to target CCR1 in mouse model of pancreatic cancer, CCR1 -/-, KC;CCR1-/-, and CCR1 inhibitor-J-113863, a potent selective CCR1 antagonist. We discovered that in the orthotopically implanted pancreatic cancer model the tumor weights in both CCR1 -/- mice and CCR1 inhibitor treated mice were smaller as compared to control groups which were wild type or receive vehicles. Further, the analysis of the tumor tissue revealed that targeting CCR1 resulted in increased cell death and downregulation of Arginase 1, an immunosuppressive molecule expressed by tumor-associated macrophage. Using KC;CCR1-/- model we found CCR1 deletion did not prevent oncogenic KRAS driven tumor initiation, however, we observed increased CD8 T cell infiltration in the tumor microenvironment. Our data points to the contributory role of CCR1 to the growth and progression of tumors in pancreatic cancer mouse models. We are currently investigating the mechanism behind it including the possibility of CCR1 in regulating tumor-associated macrophage reprograming and anti-tumor immunity in pancreatic cancer.
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences
