Targeting Autophagy to Enhance Response to Immunotherapy in Immunologically Cold Tumors – UROP Spring Symposium 2023

Targeting Autophagy to Enhance Response to Immunotherapy in Immunologically Cold Tumors

Sarah Yee

Sarah Yee photo

Pronouns: she/her

Research Mentor(s): Yuanyuan Qiao
Research Mentor School/College/Department: /
Program: RS
Session: Session 5 (2:40pm – 3:30pm)
Authors: Sarah Yee, Parth Borker, Xia Jiang, Abigail Lowe, Yang Zheng, Yi Bao, Yuanyuan Qiao

Abstract

In this project, we aimed to investigate the biology of lipid kinase PIKfyve in the progression of KRAS driven cancers, such as pancreatic cancer. To achieve this, we established pancreatic specific PIKfyve heterozygous or homozygous deletions in a KRAS genetically modified mouse model (GEMM), which included KRAS (G12D); p53 R172H; p48Cre (KPC) GEMM and KRAS (G12D); and p48 Cre (KC) GEMM. With these pancreatic cancer mouse models, we observed pancreatic lesion progression over time and compared that of mice with the presence and absence of PIKfyve. We also inspected the overall survival rate of KPC and KC mice after the deletion of PIKfyve in KPC or KC pancreatic tissue. To do so, we developed a biomarker for autophagy detection in pancreatic tissue. We analyzed tumor inhibition of a small molecule inhibitor of PIKfyve in mice using a human xenograft model and a mouse syngeneic model. In the mouse syngeneic model, we examined efficacy and immune response along with immune checkpoint blockade. After analyzing our data and observations, we found that PIKfyve slowed down the progression of pancreatic lesions for KC mice and are continuing to collect data for KPC mice.

Research Scholars

lsa logoum logo