948P - Genomic instability is associated with increased immune infiltration and PDL1 expression in epithelial ovarian cancer

Abstract

Background: High mutation load secondary to mutagenic exposures such as smoking or to mutations in mismatch DNA repair genes has been associated with increased tumor immune infiltration and response to immune therapies. Ovarian cancers (OC) demonstrate low mutation load, but high degree of genomic instability (GI) attributable to frequent defects in the homologous recombination DNA repair pathway. We sought to investigate whether GI predicted increased infiltration by tumor infiltrating lymphocytes (TILs) and PDL1 expression in OC. Methods: TILs were evaluated on FFPE OC samples and scored as percentage of stromal area. PDL1 expression was quantified as percent positive immune cells. GI was measured as the number of copy number alterations >15Mb by Oncoscan SNParray on DNA from the same FFPE samples and high GI score (GIS) defined as > median. Correlations were evaluated using a Spearman rank and differences by Mann-Whitney. Results: 66 tumor samples were evaluable for both GIS and immune infiltration. GIS and TILs showed significant variability ranging from 0 to 64 (median=28) and from 5 to 90% (median=20%) for GIS and TILs, respectively. GIS was significantly higher among high grade serous or endometrioid OC than among low grade tumors (GIS=29 vs 5; p < 0.0001) and non-significantly greater among patients with BRCA mutations and/or family history compared to wild-type OC with no family history (p = 0.12). GIS and TILs were highly correlated (R = 0.4; p = 0.0019) and median TILs were significantly increased in GIS-high vs -low tumors (29% vs 15%; p = 0.0028, Fig 1) as was immune cell PDL1 expression (p = 0.025). Fig 1 Increased TILs in tumors with high genomic instability Conclusions: High genomic instability correlated with increased tumor infiltrating lymphocytes and PDL1 expression. Whether GIS could provide a simple and predictive biomarker for immune therapies in OC should be investigated. Legal entity responsible for the study: LEARY Alexandra Funding: INCa (Institut national du cancer) Disclosure: All authors have declared no conflicts of interest.