T cells play a key role in immune-mediated glomerulonephritis, but how cytotoxic T cells interact with podocytes remains unclear. To address this, we injected EGFP-specific CD8⁺ T cells from just EGFP death inducing (Jedi) mice into transgenic mice with podocyte-specific expression of EGFP. In healthy mice, Jedi T cells could not access EGFP⁺ podocytes. Conversely, when we induced nephrotoxic serum nephritis (NTSN) and injected Jedi T cells, EGFP⁺ podocyte transgenic mice showed enhanced proteinuria and higher blood urea levels. Morphometric analysis showed greater loss of EGFP⁺ podocytes, which was associated with severe crescentic and necrotizing glomerulonephritis. Notably, only glomeruli with disrupted Bowman’s capsule displayed massive CD8⁺ T cell infiltrates that were in direct contact with EGFP⁺ podocytes, causing their apoptosis. Thus, under control conditions with intact Bowman’s capsule, podocytes are not accessible to CD8⁺ T cells. However, breaches in Bowman’s capsule, as also noted in human crescentic glomerulonephritis, allow access of CD8⁺ T cells to the glomerular tuft and podocytes, resulting in their destruction. Through these mechanisms, a potentially reversible glomerulonephritis undergoes an augmentation process to a rapidly progressive glomerulonephritis, leading to end-stage kidney disease. Translating these mechanistic insights to human crescentic nephritis should direct future therapeutic interventions at blocking CD8⁺ T cells, especially in progressive stages of rapidly progressive glomerulonephritis.

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 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. Significance: This study maps the immune response in FT precursors of HGSOC, highlighting localized IFN signaling, chromosomal instability, and competing immune surveillance and suppression along the progression axis. It provides an explorable public spatial profiling atlas for investigating precancer mechanisms, biomarkers, and early detection and interception strategies. See related commentary by Recouvreux and Orsulic, p. 1093