Mp57-02 “next-gen Sting-agonist Like Bcg Confers Enhanced Immunogenicity and Antitumor Efficacy in Vitro and in Vivo”
Year: 2019
Type: article
Abstract: GFPþ cancer cells to the muscle wall of naive FVB/NJ mice allows for the distinction of tumor cells from host cells (stromal, immune).Using defined surface antigens (CD49f, Epcam, CD44, CD24) to isolate defined lineage populations, we conducted in vivo implants to determine the potential for lineage plasticity and redistribution during bladder cancer progression.Single cell and bulk RNA sequencing analysis was used to assess the coinciding expression of multiple clinical subtypes in a single primary OHBBN bladder tumor.RESULTS: We demonstrated that: (1) OHBBN Tg(CAG-luc-eGFP) mouse bladder tumors contain lineage-defining mRNA expression subtypes identifiable in human bladder cancers including basal, luminal, p53-like, EMT & claudin and neuroendocrine.(2) Identified surface antigens that discriminate clinical mRNA subtypes in mouse tumors.(3) Identified clinically defined lineages within a single mouse bladder tumor capable of tumor initiation, lineage plasticity and redistribution to other lineage subtypes during progression and therapy.CONCLUSIONS: While clinical reports have argued that the use of a single mRNA subtype can be assigned to human bladder muscle invasive bladder cancers, our modeling argues that multiple subtypes exist and that these populations or clusters of cancer cells are dynamic both during progression and therapy.These data also have implications towards acquired resistance in clinical disease.
Source: The Journal of Urology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2921466126