Immune phenotype in high- versus low-NRF2 high grade serous ovarian cancer and the impact on prognosis

Abstract NRF2 modulates tumor immune microenvironment (IMM) in several cancers. NRF2 is activated in about 50% of high grade serous ovarian cancer (HGSOC), the most aggressive type of ovarian cancer. This study aimed to stratify HGSOC patients’ samples by NRF2 levels and identify its impact on immune phenotype and prognosis. We analyzed data from n = 7 scRNA-seq, n = 365 RNA-seq of human HGSOC samples, and n = 240 HGSOC samples from a tumor microarray (TMA). Results showed human HGSOC samples can be classified by NRF2High and NRF2Low tumors. RNA-seq data analysis along with IHC labeling showed that NRF2High HGSOCs are enriched with hallmarks of immune suppressive markers (ISMs). Specifically, NRF2High tumors are identified as tumors associated macrophages (TAMs) with worst survival (p = 0.038) was observed in CD68High tumors. NRF2Low tumors were enriched with immune activated markers such as CD3E and CD80 with a prognostic significance. Immune checkpoints (ICs) are important in both groups. However, their levels and spatial distribution are the factors that define their impact on prognosis in these samples. This study is the first that shows classification of HGSOC based on NRF2 levels and suggests IHC-labeling and genomic evaluation of NRF2 and immune markers in HGSOC to predict prognosis.