Abstract 4597: Globo H affects the immune tumor microenvironment in cholangiocarcinoma

Background: Cholangiocarcinoma (CCA), which is characterized by aberrant glycosylation on the surface, is a rapidly progressing cancer with an unsatisfactory response to chemoimmunotherapy. Globo H (GH) ceramide, a tumor-promoting glycosphingolipid, is expressed in various types of cancer and is correlated with poor prognosis. However, few studies have discussed the role of GH in CCA. Hence, the pathways involved and alterations in the immune tumor microenvironment (TME) have not been explored. Methods: We aimed to reveal the clinical features and immune modulatory role of tumor GH and its correlation in CCA. We evaluated the signaling-associated proteins and those coexpressed with GH. Tumor-infiltrating immune cells (TIMCs) were compared between tumors with high vs. low levels of GH synthesizing enzyme (GH-se) using open-domain databases and single-cell RNA sequencing results. Results: Surface GH expression correlated with poor prognosis and peritumor inflammation. High-GH CCA cells coexpressed GH with PD-L1, EGFR and EPCAM. While GH and its synthesizing enzymes affected immune modulation and survival, TIMCs such as neutrophils, tumor-associated macrophages, natural killer cells and foxp3 regulatory T cells were significantly altered in high-GH-se tumors. Conclusion: Tumor GH expression correlates with a poor prognosis in patients with cholangiocarcinoma. GH modulates the immune TME by promoting an immune-evasive niche. The results provide insights for combining immunotherapy with GH-targeting therapy. Citation Format: Chih Chieh Yen, Tzer Min Kuo, Chun Jung Lin, Hung Wen Tsai, Wen Lung Wang, Chien Jui Huang, Ping Jui Su, Ting Kai Liao, I Ting Liu, Li Chin Cheng, Ying Jui Chao, Yan Shen Shan, Chia Jui Yen, Ming Tain Lai. Globo H affects the immune tumor microenvironment in cholangiocarcinoma [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 4597.