Figure 1. Efficacy of PARP inhibition depends on recruitment of CD8⁺ T cells.

(A) Tumor chunks from the BRCA GEMM were transplanted in syngeneic FVB/129P mice (8–10/group), which were treated with vehicle or olaparib along with an isotype (iso) control or an anti-CD8 antibody. Median survivals are shown in parentheses. Tumors were also transplanted in SCID mice (5–6/group) and treated with vehicle or olaparib. Statistical analysis was performed using the Log-rank (Mantel-Cox) test. (B-C) Vehicle (VEH) and olaparib (OLA)-treated tumors were harvested 5 days post-treatment, fixed and subjected to immunohistochemical analysis for CD3, CD8 and granzyme B expression. Staining was quantified using Aperio algorithms. Error bars represent standard deviation (SD). Statistical analyses were performed using unpaired t-tests or unpaired t-tests with Welch’s correction if variances were significantly different. Representative images are shown at 20X magnification. Scale Bar, 200 μm. (D-E) Tumors from vehicle or olaparib-treated mice (n=9) were harvested 5 days post-treatment and analyzed by flow cytometry. Scatter plots show significant increases in CD45⁺, CD3⁺, CD8⁺ and granzyme B⁺ cells in olaparib-treated animals. Pie charts show the proportions of different cell types (as % of total live events) in the tumor microenvironment. Error bars represent SD. Statistical analyses were performed using unpaired t-tests or unpaired t-tests with Welch’s correction. (F) Immunoblotting for BRCA1 expression in KB1P-G3 and KB1P-G3+BRCA1 cells. (G) KB1P-G3 and KB1P-G3+BRCA1 tumors from 5 vehicle- or olaparib-treated mice were harvested 5 days post-treatment and analyzed by flow cytometry. Scatter plots show % CD3⁺, CD8⁺ and granzyme B⁺ cells. Error bars represent SD. Statistical analyses were performed using two-way ANOVA with Sidak’s post-hoc test.