High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC. Our findings reveal immune modulating mechanisms within precursor epithelium, characterized by chromosomal instability, persistent interferon (IFN) signaling, and dysregulated innate and adaptive immunity. FT precursors display elevated expression of MHC-class I, including HLA-E, and IFN-stimulated genes, typically linked to later-stage tumorigenesis. These molecular alterations coincide with progressive shifts in the tumor microenvironment, transitioning from immune surveillance in early STICs to immune suppression in advanced STICs and cancer. These insights identify potential biomarkers and therapeutic targets for HGSOC interception and clarify the molecular transitions from precancer to cancer.
Keywords: HLA-A; HLA-E; High Grade Serous Ovarian Carcinoma; Natural Killer cells; Ovarian cancer; Serous Tubal Intraepithelial Carcinoma; antigen presentation; cancer progression; fallopian tube; homologous recombinant deficient tumor; innate immune system; multi-plex imaging; p53 signatures; preneoplasia; single cell; spatial transcriptomics; tumor immune interaction; tumor microenvironment.