Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma
Cancer Discovery. 2025;15(6):1180-1202. DOI 10.1158/2159-8290.CD-24-1366. PMID 39704522. PMCID PMC12130810.
How to cite
AMA
Kader T, Lin JR, Hug CB, Coy S, Chen YA, de Bruijn I, et al. Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma. Cancer Discov. 2025;15(6):1180-1202. doi:10.1158/2159-8290.CD-24-1366APA
Kader, T., Lin, J. R., Hug, C. B., Coy, S., Chen, Y. A., de Bruijn, I., et al. (2025). Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma. Cancer Discovery, 15(6), 1180-1202. https://doi.org/10.1158/2159-8290.CD-24-1366BibTeX
@article{kader2025multimodal,
title = {Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma},
author = {Kader, Tanjina and Lin, Jia-Ren and Hug, Clemens B. and Coy, Shannon and Chen, Yu-An and de Bruijn, Ino and others},
journal = {Cancer Discovery},
year = {2025},
volume = {15},
number = {6},
pages = {1180--1202},
doi = {10.1158/2159-8290.CD-24-1366},
pmid = {39704522}
}High-grade serous ovarian cancer is usually caught late and is hard to treat. It does not begin in the ovary: the earliest lesions arise in the lining of the fallopian tube and creep toward invasive disease over years. How the immune environment shifts across that hidden progression was poorly mapped.
The team built a spatial atlas of 44 fallopian-tube specimens from 43 people, pairing single-cell protein imaging of intact tissue with region-level gene readouts. Early precursor lesions already showed an active interferon response and signs of DNA damage. As lesions advanced, natural-killer cells and one dendritic-cell type thinned out, macrophages expanded, and T cells drifted toward exhaustion.
The map pins down when and where the fallopian-tube microenvironment turns immunosuppressive, well before invasive cancer takes hold.
Key findings
- A 31-antibody CyCIF atlas resolved single cells across the full fallopian-tube-to-cancer progression. Whole-slide cyclic immunofluorescence phenotyped all 44 specimens from 43 individuals — spanning benign p53 signatures, intraepithelial carcinoma and invasive high-grade serous ovarian carcinoma — while every cell kept its position in intact tissue.
- Interferon-pathway activation rose stepwise as precursor lesions advanced toward cancer. The share of epithelial cells expressing IFN markers such as p-TBK1, p-STATs and HLA-A/E climbed from a median of 22% in the earliest p53 signatures to 33% in intraepithelial carcinoma and 43% in lesions co-occurring with invasive cancer.
- Early immune surveillance gave way to a suppressive microenvironment as lesions progressed. Cross-referencing the imaging with region-level spatial transcriptomics, natural-killer cells and cDC1 dendritic cells present in early precursors declined with progression, while CD68+ and CD163+ macrophages expanded to their highest levels in the 24 invasive cancers.
CyteFinder in the methods
“Images were acquired using a 20× objective (0.75 NA) on a CyteFinder slide scanning fluorescence microscope (RareCyte Inc.).”
— Kader et al., Cancer Discovery (2025), Methods, “2D CyCIF”
Disclosure: RareCyte is named in the competing-interests statement of the publication cited above.
Why it matters for CyteFinder users
If you are weighing the CyteFinder for a tissue study, look closely at the job it did here. This was a multimodal atlas: a spatial-transcriptomics arm read gene activity across tissue regions, but that measurement cannot say which individual cells carry a protein or where they sit. That is the question the CyteFinder answered. The authors ran 31-plex cyclic immunofluorescence on intact FFPE fallopian-tube and ovarian sections, staining lineage and functional markers across successive rounds, then acquired each cycle on the instrument and registered them into one whole-slide image. From that image they phenotyped single cells across all 44 specimens, traced interferon-pathway activation rising from precursor to cancer, and followed how natural-killer cells, dendritic cells, macrophages and T cells reorganized as lesions progressed. For your own work the point is concrete: when a question turns on which cells express a marker and who their neighbors are in tissue you cannot dissociate, whole-slide cyclic imaging is the measurement that answers it, at single-cell resolution across every specimen in the study.
