| First Author | Saito R | Year | 2018 |
| Journal | Cancer Res | Volume | 78 |
| Issue | 14 | Pages | 3954-3968 |
| PubMed ID | 29784854 | Mgi Jnum | J:264280 |
| Mgi Id | MGI:6195998 | Doi | 10.1158/0008-5472.CAN-18-0173 |
| Citation | Saito R, et al. (2018) Molecular Subtype-Specific Immunocompetent Models of High-Grade Urothelial Carcinoma Reveal Differential Neoantigen Expression and Response to Immunotherapy. Cancer Res 78(14):3954-3968 |
| abstractText | 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-Cre(ERT2); Trp53(L/L); Pten(L/L); Rosa26(LSL-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. (c)2018 AACR. |
