Development of human pancreatic cancer avatars as a model for dynamic immune landscape profiling and personalized therapy.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, a disease with dismal overall survival. Advances in treatment are hindered by a lack of preclinical models. Here, we show how a personalized organotypic "avatar" created from resected tissue allows spatial and temporal reporting on a complete in situ tumor microenvironment and mirrors clinical responses. Our perfusion culture method extends tumor slice viability, maintaining stable tumor content, metabolism, stromal composition, and immune cell populations for 12 days. Using multiplexed immunofluorescence and spatial transcriptomics, we identify immune neighborhoods and potential for immunotherapy. We used avatars to assess the impact of a preclinically validated metabolic therapy and show recovery of str

SUBMITTER: Hughes D 

PROVIDER: S-EPMC11225792 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature