Fig. 7
From: Single-cell multi-omics uncovers CPS1 as a breast cancer immune evasion therapeutic target
CPS1 knockdown enhances anti-tumor immunity and synergizes with anti-PD1 therapy in a mouse breast cancer model. (A) Schematic of the experimental design. C57BL/6 J mice were subcutaneously injected with E0771 cells (shNC or shCPS1, 5 × 105 cells). Anti-PD1 (200 μg/mouse) or control treatments were administered intraperitoneally on days 7, 12, and 16. Tumor growth and immune responses were assessed on day 21. (B) Representative images of excised tumors from the four treatment groups: shNC, anti-PD1, shCPS1, and shCPS1 + anti-PD1. Tumor size is visibly reduced in the shCPS1 + anti-PD1 group compared to the other groups. (C) Tumor growth curves showing a significant reduction in tumor volume in the shCPS1 + anti-PD1 group compared to single treatments or controls (p < 0.0001). (D) Kaplan–Meier survival curve illustrating improved survival in the shCPS1 + anti-PD1 group compared to the other groups (p < 0.0001). (E) Tumor weight at the endpoint. The shCPS1 + anti-PD1 group exhibits the lowest tumor weight (p < 0.0001). (F–H) Flow cytometry analysis of tumor-infiltrating immune cells: (F) Percentage of CD4+ T cells among CD45+ immune cells. (G) Percentage of CD8+ T cells among CD45+ immune cells. (H) Percentage of Ki67+ proliferating CD8+ T cells among tumor-infiltrating CD8+ T cells. The shCPS1 + anti-PD1 group shows significantly enhanced infiltration and activation of CD8+ T cells (p < 0.0001). (I-J) Flow cytometry analysis of IFN-γ+ CD8+ T cells in tumors. Representative plots (I) and quantification (J) demonstrate increased IFN-γ production in CD8+ T cells from the shCPS1 + anti-PD1 group (p < 0.0001). (K-L) Flow cytometry analysis of GZMB+ CD8 + T cells in tumors. Representative plots (K) and quantification (L) show significantly increased cytotoxic CD8+ T cells in the shCPS1 + anti-PD1 group (p < 0.0001).
