GSE174540 Characterization of a novel mouse model of undifferentiated pleomorphic sarcoma that is lymphocyte poor, macrophage rich, and resistant to immune checkpoint blockade

Contributors : Karys M Hildebrand ; Kayla L Marritt ; Kurt N Hildebrand ; Arvind K Singla ; Reid McNeil ; Franz Zemp ; Jahanara Rajwani ; Doha Itani ; Pinaki Bose ; Douglas J Mahoney ; Frank R Jirik ; Michael J MonumentSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusSarcomas are rare, difficult to treat, mesenchymal lineage tumours that disproportionately affect children and young adults. Immunologically-based therapies have improved outcomes for numerous adult cancers, however, such approaches have proven ineffective for the majority of individuals with advanced sarcomas. Clinically relevant, immunologically-competent, and transplantable pre-clinical sarcoma models are needed in order to test and develop novel immunologically-based therapies for sarcoma. Herein we show that Cre- lox P-mediated simultaneous activation of Kras G12D , and deletion Trp53, in the hindlimb muscles of C57Bl/6 mice results in the development of highly penetrant, rapid onset undifferentiated pleomorphic sarcomas (UPS). The latter represents a model one of the most common human sarcoma subtypes both histologically and genetically. Furthermore, cell lines derived from the UPS tumors induced in C57Bl/6 mice can be transplanted into the hindlimbs or lungs of na ïve, immune competent syngeneic mice. Immunological characterization of both the spontaneous and transplanted UPS tumours demonstrates an immunologically- ‘quiescent’ microenvironme...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research