BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer

Checkpoint molecules such as programmed cell death protein-1 (PD-1) and its ligand PD-L1 are critically required for tumor immune escape. The objective of this study was to investigate tumoral and mRNA-expression in a cohort of ovarian cancer (OC) patients in relation to tumor mutations. We analyzed mRNA expression of , and by quantitative real-time PCR in tissue of 170 patients with low grade-serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared to 28 non-diseased tissues (ovaries and fallopian tubes) in relation to tumor protein 53 ( ) and breast cancer gene 1/2 ( ) mutation status. -mutated OC strongly expressed compared to wild-type OC ( = 0.028) and -mutated OC increasingly expressed ( = 0.024) and ( = 0.012) compared to wild-type OC. For the first time in human, we noted a strong correlation between tumoral and or mRNA-expression, respectively ( < 0.001). OC tissue increasingly expressed compared to healthy controls (vs. ovaries: < 0.001; vs. tubes: = 0.018). and mRNA-expression increased with higher tumor grade ( = 0.008 and = 0.027, respectively) and younger age (< median age, = 0.001). Finally, in the major subgroup of our cohort, FIGO stage III/IV HGSOC, high and mRNA-expression was associated with reduced progression-free ( = 0.024) and overall survival ( = 0.049) but only in the univariate analysis. Our study suggests that in OC / mRNA-expression is controlled by and affected by and mutations. We suggest that these mutations might serve as potential predictive factors that guide anti- / immunotherapy.