Abstract 5206: High level STING expression in tumor and inflammatory cells is linked to microsatellite instability and favorable tumor parameters in a cohort of 1,900 colorectal cancer patients

Abstract Background: The stimulator of interferon genes (STING) is a transmembrane protein expressed on a variety of cell types including epithelial, inflammatory (lymphocytes and macrophages), and endothelial cells. STING expression has been described at variable levels in various tumor types where it might enhance anti-tumoral effects of the immune system and impact tumor angiogenesis. STING activating targeted therapies are currently evaluated in preclinical studies. However, the clinical significance of STING expression in tumor cells as compared to tumor-associated inflammatory cells is not fully resolved. Methods: To evaluate the potential clinical significance of STING expression in different cell types of colorectal cancer (CRC) tissue (tumor cells, lymphocytes, macrophages and endothelial cells), more than 1,900 patients were analyzed by multiplex fluorescence immunohistochemistry (CKpan, STING, CD45, CD68 and CD31) in a tissue microarray format (TMA) in combination with a deep-learning based algorithm for automated cell detection. Results: STING expression on colorectal cancer cells varied markedly. Of 1,905 evaluable cancers, 601 (31.5%) showed a strong expression in virtually all tumor cells and 428 (22.5%) lacked STING staining while 478 (25.1%) showed a weak, and 398 (20.9%) a moderate staining. High STING expression on tumor cells was associated with microsatellite instability (MSI, p<0.0001), low tumor stage (p=0.0013), absence of nodal metastasis (pN0, p=0.0003) and tumor localization in the right colon (p<0.0001). A multivariate analysis revealed that these associations were solely driven by the tight relationship between STING expression in tumor cells and MSI. Accordingly, subgroups of tumors with and without MSI lacked significant associations between STING expression on tumor cells and pT or pN categories. While the total number of lymphocytes and macrophages were related to MSI, low pT, and pN0, there were significant associations between a high percentage of STING positive macrophages and lymphocytes to low pT stage (p<0.0001 each) and absence of nodal metastases for high percentage of STING positive macrophages (p=0.0033). STING was regularly expressed on endothelial cells of small vessels. Although the intensity appeared to be variable, there was no link to tumor phenotype. Conclusion: In summary, the significant link between high STING expression on tumor cells, lymphocytes and macrophages with a favorable tumor phenotype supports the concept of STING representing an enhancer of anti-tumoral effects of the immune system. Citation Format: Elena Bady, Zhihao Huang, Maximilian Lennartz, Claudia Hube-Magg, Julia Ebner, Frank Jacobsen, Stefan Steurer, Christian Bernreuther, Till S. Cauditz, Andreas H. Marx, Till Krech, Eike Burandt, Guido Sauter, Ronald Simon, Sarah Minner, Jan Hendrik Mueller. High level STING expression in tumor and inflammatory cells is linked to microsatellite instability and favorable tumor parameters in a cohort of 1,900 colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5206.