Abstract 5860: Stimulator of interferon genes protein (STING) expression in tumor cells is linked to favorable disease parameters and a high density of tumor infiltrating inflammatory cells in urinary bladder cancer

Abstract STING is a key element in the cGAS/STING cytosolic DNA sensing pathway which can stimulate immune response through type I interferon (IFN) production. Numerous STING agonists are currently evaluated for their suitability as anticancer drugs. Most previous studies focused on STING expression in inflammatory cells, but STING can also be expressed in cancer cells. To evaluate the potential clinical significance of STING expression in bladder cancer cells, STING was analyzed by immunohistochemistry in more than 2,500 urothelial bladder carcinomas in a tissue microarray format. STING staining in tumor cells occurred in 59.1% of urothelial carcinomas including 31.1% with weak, 11.6% with moderate, and 16.3% with strong staining. Detectable STING expression in tumor cells was associated with histo-pathological features of favorable disease course including absence of invasion (p<0.0001), low grade in pTa (p<0.0001) and in pT2-4 (p=0.0018) tumors, pN0 (p=0.0036), L0 (0.0084), and V0 (0.0006) status in pT2-4 cancers, but was not significantly associated with overall, recurrence-free and tumor specific survival. A comparison with previously collected immune cell parameters revealed significant associations between high STING expression in tumor cells and high numbers of tumor infiltrating lymphocytes including various T-cells populations (CD8: p<0.0001, CD4: p=0.0462, FOXP3: p=0.0001), macrophages (M1: p=0.00003, M2: p<0.0001), dendritic cells (p<0.0001), and PD-L1 expression on tumor cells (p<0.0001). It is concluded that high STING expression of tumor cells is strongly linked to a high density of tumor infiltrating inflammatory cells which is most likely causative for the significant associations with favorable disease parameters. Given the abundant presence of STING in immune cell rich urothelial cancers, STING agonists may exert significant effects in STING positive cancers. Citation Format: Bisan A. Zohud, Qi Fang, Clara Tenkerian, Tim Thoenissen, Jisheng Chen, Johannes Schloderer, Zoltán Winter, Philip Eichhorn, Susanne Merkel, Renato Liguori, Fulvia Ferrazzi, Florian R. Greten, Tobias Bäuerle, Marc P. Stemmler, Thomas Brabletz, Rene Jackstadt, Claudia Günther, Michael Stürzl, Elisabeth Naschberger. Stimulator of interferon genes protein (STING) expression in tumor cells is linked to favorable disease parameters and a high density of tumor infiltrating inflammatory cells in urinary bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5860.