SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in ovarian cancer

Abstract

Large independent analyses on cancer cell lines followed by functional studies have identified Schlafen 11 (SLFN11), a putative DNA/RNA helicase, as the strongest predictor of sensitivity to DNA-damaging agents. However, its role as a prognostic biomarker is undefined, partially due to the lack of validated methods to score SLFN11 in human tissues. Here, we implemented a pipeline to quantify SLFN11 in human cancer samples. By analyzing a cohort of high-grade serous ovarian carcinoma specimens prior platinum-based chemotherapy treatment, we demonstrate that SLFN11 is expressed by infiltrating innate and adaptive immune cells. We show, for the first time, that SLFN11 density in both the neoplastic and microenvironmental components was independently associated with favorable outcome. Transcriptomic analyses suggested the presence of a hitherto modulation of the cancer-immunity cycle orchestrated by SLFN11. We propose SLFN11 as a dual biomarker capturing simultaneously interconnected immunological and cancercell-intrinsic functional dispositions associated with sensitivity to DNA damaging agents.