LAUSR

High‐grade serous ovarian carcinoma (HGSOC) associates with the worst patient outcome. Understanding the tumor environment in terms of quantifying endogenous retroviruses (ERVs) and LINE‐1 expression and their correlations with inflammation genes, checkpoint inhibitors and patient survival is needed. Analysis of 102 treatment‐naïve HGSOC and control tissues for ERVs, LINE‐1, inflammation and immune checkpoints identified five clusters with diverse patient recurrence‐free survivals. One cluster termed Triple‐I with the best patient survival showed the highest number of tumor infiltrating lymphocytes along with 22 overexpressed genes, including CXCL9 and AIM2. However, Triple‐I associated with the lowest ERV/LINE‐1 expression. The tumor cluster with the second‐best patient survival had both high ERV/LINE‐1 expression and inflammation. Multiplex‐immunohistochemistry revealed CD28 protein solely on immune cells, without co‐expression of the inhibitory CTLA4 receptor. The largest tumor cluster with high ERV/LINE‐1 expression but low inflammation showed a significant low gene expression of the dsRNA sensors MDA5 and RIG‐I supporting an aberrant block in IFN signaling. Our study represents an intrinsic ‘molecular and immunological snapshot’ of the HGSOC tumor environment important for understanding retroelements and inflammation for clinical relevance.