| Autor: |
William Y. Kim, Benjamin G. Vincent, Scott E. Williams, Jeffrey S. Damrauer, Kevin M. Byrd, Ujjawal Manocha, Shengjie Chai, Kyle G. Stewart, Sara E. Wobker, Jordan Kardos, Lisa M. Bixby, Takanobu Utsumi, Christof C. Smith, Ryoichi Saito |
| Rok vydání: |
2023 |
| DOI: |
10.1158/0008-5472.c.6510351.v1 |
| Popis: |
High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like and basal-like subtypes. We describe here the first subtype-specific murine models of bladder cancer and show that Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL, luminal-like) and BBN (basal-like) tumors are more faithful to human bladder cancer than the widely used MB49 cells. Following engraftment into immunocompetent C57BL/6 mice, BBN tumors were more responsive to PD-1 inhibition than UPPL tumors. Responding tumors within the BBN model showed differences in immune microenvironment composition, including increased ratios of CD8+:CD4+ and memory:regulatory T cells. Finally, we predicted and confirmed immunogenicity of tumor neoantigens in each model. These UPPL and BBN models will be a valuable resource for future studies examining bladder cancer biology and immunotherapy.Significance: This work establishes human-relevant mouse models of bladder cancer. Cancer Res; 78(14); 3954–68. ©2018 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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