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. Author manuscript; available in PMC: 2019 Feb 7.
Published in final edited form as: Cell Rep. 2018 Dec 11;25(11):2972–2980.e5. doi: 10.1016/j.celrep.2018.11.054

Figure 1. Therapeutic Efficacy of Olaparib and PD-1 Blockade in a Brca1-Null GEMM of HGSOC.

Figure 1.

(A) Genetic loss of Tp53 and Brca1 and amplification and overexpression of Myc co-occur in HGSOC in clinical samples (The Cancer Genome Atlas [TCGA] database).

(B) Generation of a Brca1-null genetically engineered mouse model (GEMM) of HGSOC (Trp53−/−,Brca1−/−,Myc; termed PBM). A representative H&E staining shows serous carcinoma nature of the PBM tumor. Scale bar, 25 μm.

(C) GSEA showing upregulated immune response and T cell activation in olaparib-treated PBM tumors. Nominal p < 0.001, false discovery rate q < 0.001.

(D) Orthotopically transplanted PBM tumors in Rag1−/− or wild-type (WT) mice treated with olaparib or vehicle control (WT, n = 6/group; Rag1−/−, n = 5/group).

(E) PBM tumor-bearing FVB mice were treated with olaparib with or without an anti-CD8 neutralizing antibody (n = 8 tumors per group).

(F) Experimental scheme (top) and representative bioluminescence imaging analysis of mice bearing orthotopic PBM tumor allografts (luciferized) treated with various agents as indicated after 21 days of treatment.

(G) Tumor burden of PBM tumor-bearing mice treated with indicated agents was measured by bioluminescence (number of analyzed mice is indicated in the brackets).

In (D), (E), and (G), tumor burden is quantified by the intensity of bioluminescence signal in the regions of interest (ROIs) determined at each imaging time point. Arrows indicate treatment start date. Data are represented as mean ± SEM. *p < 0.05, **p < 0.01, and ***p < 0.001.