biostudies-literatureKader TCanary FoundationBWH President’s Scholar awardLudwig Center at HarvardHonorable Tina Brozman Foundation (Tina's Wish)Dr. Miriam and Sheldon G. Adelson Medical Research FoundationDivision of Cancer Prevention, National Cancer Institute (DCP, NCI)U.S. Department of Defense (DOD)Program for Interdisciplinary Neuroscience (PIN)Gray FoundationBridge Project between the Koch Institute at MIT and DC/HCCBWH President's Scholar awardNational Cancer Institute (NCI)Canary Foundation (THE CANARY FUND)Carl H. Goldsmith Ovarian Cancer Translational Research FundThe Mike and Patti Hennessy FoundationDr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF)U.S. Department of DefenseNational Cancer InstituteNCI NIH HHSDivision of Cancer Prevention, National Cancer InstituteProgram for Interdisciplinary NeuroscienceHonorable Tina Brozman FoundationLudwig Center at Harvard (Ludwig Center)1180-1202https://www.ebi.ac.uk/biostudies/studies/S-EPMC12130810biostudies-literatureUnknown15(6)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 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 Cancer discoveryMultimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.PMC12130810U2C-CA233262W81XWH-22-1-0852R50-CA274277P50-CA228991P30 CA008748U54 CA268072U01-CA284207P50 CA228991R50 CA274277U01 CA284207U54-CA268072Chen YACoy SSatravada BAGysler SMShih NLee JSSantagata SHeath JRKim SHSchultz NHug CBChan Sde Bruijn IYapp CSorger PKJung EKader TDrapkin RMuhlich JLMingo GTefft JBLopez Leon MOmran DKPelletier RJDrescher CWAgudo JLin JRKundra RXu YfalseMultimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.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 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 2025-01-01T00:00:00Z2025 Jun2026-06-02T02:41:42.009Z2026-04-13T03:12:16.241ZS-EPMC121308103970452210.1158/2159-8290.CD-24-1366