Abstract 7640: Ciliated cells drive critical STING-mediated tumor suppression in fallopian tube epithelium

Abstract Mitigating DNA damage in the fallopian tube epithelium (FTE) is essential for preventing tubo-ovarian high-grade serous carcinoma (HGSC). Here we demonstrate that STING is abundantly expressed in the ciliated cells of the FTE and functions as a critical immune-independent tumor suppressor. Using patient samples, mouse models, and organoid systems, we demonstrate that ciliated cells mount a dual protective response to ovulation-associated genotoxic stress: intrinsic STING-driven apoptosis and extrinsic clearance of neighboring damaged secretory cells via TNFα secretion. This surveillance mechanism markedly limits DNA damage accumulation within the epithelial microenvironment. Crucially, while these mechanisms are vital for maintaining homeostasis and reducing genomic instability, they fail to impact p53-deficient precursor lesions as both intrinsic and extrinsic pro-apoptotic processes rely on functional p53 signaling. This study uncovers a previously unrecognized, immune-independent role for STING-high ciliated fallopian tube cells as active guardians of genomic integrity, whose loss creates a permissive niche for HGSC initiation. CONFLICT OF INTEREST STATEMENT: R.D. serves on the scientific advisory board of VOC Health and Repare Therapeutics. DGH is a previous founder and Chief Medical Officer of Imagia Canexia Health. The other authors declare that they have no competing interests. Citation Format: Jose Colina, Maria Sol Recouvreux, Alex Sobeck, Benjamin K. Johnson, Yinzhi Lin, Sreeja C. Sekhar, Rita A. Avelar, Gabriela Rivera, Yali Zhai, amber fatima, Paula DiBenedetto, Justin Baldassarre, Grace McIntyre, Jessica Teitel, Michele Cusato, Harini Ram, Noah Puleo, Karan Bedi, Jane Miglo, Hui Shen, Dafydd G. Thomas, Jutta Huvila, Dawn R. Cochrane, Ronny I. Drapkin, Yu Lei, Joanna E. Burdette, David G. Huntsman, Kathleen Cho, Sandra Orsulic, Analisa DiFeo. Ciliated cells drive critical STING-mediated tumor suppression in fallopian tube epithelium abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7640.