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Updated: May 7, 2026
Immunophenotyping of Orthotopic Homograft Syngeneic of Murine Primary KPC Pancreatic Ductal Adenocarcinoma by Flow Cytometry
Published on: October 9, 2018
Development of human pancreatic cancer avatars as a model for dynamic immune landscape profiling and personalized
Daniel Hughes1, Alice Evans1, Simei Go1
1Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
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 stromal and immune phenotypes and tumor redifferentiation. To determine clinical relevance, we monitored avatar response to gemcitabine treatment and identify a patient avatar-predictable response from clinical follow-up. Thus, avatars provide valuable information for syngeneic testing of therapeutics and a truly personalized therapeutic assessment platform for patients.
Insights
Personalized pancreatic cancer "avatars" from patient tissue maintain tumor microenvironments for 12 days. These pancreatic ductal adenocarcinoma models predict clinical responses to therapies, aiding drug development.
Area of Science:
- Oncology
- Translational Research
- Cancer Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) has poor survival rates.
- Limited preclinical models hinder therapeutic advancements.
- A need exists for models reflecting the in situ tumor microenvironment.
Purpose of the Study:
- To develop and validate personalized organotypic tumor avatars from patient tissue.
- To assess the utility of these avatars for preclinical drug testing and personalized therapy assessment.
Main Methods:
- Created personalized organotypic "avatars" from resected pancreatic tumor tissue.
- Utilized perfusion culture to maintain slice viability for 12 days.
- Employed multiplexed immunofluorescence and spatial transcriptomics for analysis.
Main Results:
- Avatars maintained stable tumor content, metabolism, stroma, and immune cell populations.
- Identified immune neighborhoods and immunotherapy potential.
- Assessed metabolic therapy impact and predicted gemcitabine response, correlating with clinical outcomes.
Conclusions:
- Organotypic avatars accurately mirror the in situ tumor microenvironment.
- Avatars serve as a valuable platform for syngeneic drug testing.
- This personalized approach offers a new avenue for therapeutic assessment in pancreatic cancer.
