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

JCI Insight. 2021 Sep 22;6(18):e146098. doi: 10.1172/jci.insight.146098.


Large independent analyses on cancer cell lines followed by functional studies have identified Schlafen 11 (SLFN11), a putative helicase, as the strongest predictor of sensitivity to DNA-damaging agents (DDAs), including platinum. 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 (HGSOC) specimens before platinum-based chemotherapy treatment, we show, for the first time to our knowledge, that SLFN11 density in both the neoplastic and microenvironmental components was independently associated with favorable outcome. We observed SLFN11 expression in both infiltrating innate and adaptive immune cells, and analyses in a second, independent, cohort revealed that SLFN11 was associated with immune activation in HGSOC. We found that platinum treatments activated immune-related pathways in ovarian cancer cells in an SLFN11-dependent manner, representative of tumor-immune transactivation. Moreover, SLFN11 expression was induced in activated, isolated immune cell subpopulations, hinting that SLFN11 in the immune compartment may be an indicator of immune transactivation. In summary, we propose SLFN11 is a dual biomarker capturing simultaneously interconnected immunological and cancer cell-intrinsic functional dispositions associated with sensitivity to DDA treatment.

Keywords: Bioinformatics; Cancer; Cell Biology; Cellular immune response; Oncology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cisplatin / therapeutic use
  • Databases, Genetic
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunity, Innate
  • Lymphocyte Count
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Macrophages / immunology
  • Middle Aged
  • Neoplasm Grading
  • Neoplasms, Cystic, Mucinous, and Serous / drug therapy*
  • Neoplasms, Cystic, Mucinous, and Serous / immunology*
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Progression-Free Survival
  • RNA / metabolism
  • Tumor Microenvironment


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Nuclear Proteins
  • SLFN11 protein, human
  • RNA
  • Cisplatin

Grants and funding

PostDoc Fellowship funding and Bioscience Early Oncology Funding