Investigating the effects of IFN-gamma on attached and detached ovarian cancer cells

The interplay between intrinsic and niche-driven mechanisms that enables DTCs to survive and home to distant organs remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) coupled with velocity analyses in ascites and metastasis-bearing omenta uncovered an emergent and distinct interferon-gamma centric transcriptional trajectory, enriched among early seeding clones. Knockout of IFN-gamma receptor 1 (Ifngr1) in tumor cells significantly reduced metastatic burden and extended survival, underscoring the importance of tumor cell intrinsic IFN-gamma signaling in ovarian cancer metastasis. We identified that the tumor intrinsic IFN-gamma response and ascites-derived tumor-associated macrophages (TAMs) protect cancer cells from anoikis-mediated death. To investigate the mechanism underlying increased cancer cell survival under IFN-gamma treatment and ULA conditions, we performed bulk RNA-sequencing. We discovered increased expression of the anti-apoptotic gene Parp14 in cancer cells treated with IFN-gamma, specifically under ultra low attachment conditions.