Poster 1016: Investigating the TME through PDX RNAseq Analysis

Transcriptomic Analysis of Bulk Tissues from a Large PDX Collection as a Novel Platform for Discovering New TME Targets/Drugs

Jia Xue, Wubin Qian, Sheng Guo, Annie An, Davy Ouyang, and Henry Q. Li

Cancers are collections of diverse diseases, of both genetic and immunological abnormalities. The heterogeneous tumor microenvironment (which includes immune components) and its interaction with tumor cells plays a critical role in tumor progression and in response to anticancer agents, particularly immunotherapies.

However, investigating TME-specific components is particularly challenging due to the difficulty in separating stroma from tumor cells, either physically via microdissection or in silico via bioinformatics.

This poster investigates patient-derived xenograft (PDX) models as a new system to investigate the TME, where human and mouse content can readily be separated in silico. Approximately 1600 bulk tumor tissues from PDX grown in athymic mice have been sequenced for this analysis.

Read this Poster to Discover:

• The identification of all types of adaptive and innate immune cells in mouse stroma and a variety of human immune components, with corresponding fractions varying across cancer subtypes and individual models
• The large number of intra-species interactions and a smaller number of inter-species interactions identified by co-regulation analysis, and the reverse correlation between number of interactions and percent take rate across PDX collections
• A potential role for KRAS mutation in tumor growth independency on TME, demonstrated by highest take rate/lowest interaction number in pancreatic cancer (which has high KRAS mutation rate), and confirmed in KRAS mutant CRC vs wild type

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