Abstract 5911: The role of CD53+ subsets and the JAK/STAT3 pathway in regulating cancer stemness and immune escape in esophageal squamous cell carcinoma

T cell therapy has revolutionized treatment for hematologic malignancies but faces significant challenges in solid tumor applications, including esophageal squamous cell carcinoma (ESCC). In this study, we utilized a dynamic subcutaneous tumor growth model in mice to investigate how ESCC tumors modulate T cell activity through four distinct phases: initial enlargement, reduction, stabilization, and explosive growth. Single-cell sequencing revealed that CD53+ subsets were enriched in the reduction stage and showed their function in stemness regulation and immune escape. Functionally, CD53+ mouse ESCC cell lines showed a higher organoid formation ability when compared with CD53- cells. When co-cultured with T cells, CD53+ ESCC cell lines revealed their capability in regulating T cell exhaustion. Mechanically, GO enrichment analysis and western blotting demonstrated that CD53+ cells activated IL-6/JAK/STAT3 signaling pathways and upregulated their downstream genes such as C-myc and PD-L1. Furthermore, in vivo study showed that JAK inhibitor Ruxolitinib and STAT3 inhibitor C188-9 could efficiently reduce tumor growth and enhance T cell infiltration in CD53+ mouse ESCC cell lines, suggesting a role in tumor proliferation and T cell editing. This study aims to elucidate the biological function of CD53+ subset ESCC cells in tumor progression and verify their role in T cell regulation, offering new therapeutic targets for ESCC treatment. Citation Format: Beilei Liu, Hongyu Zhou, Licheng Tan, Bowen Yao, Shuang Zhang, Jiayi Huang, Mengsu Yang, Xinyuan Guan. The role of CD53+ subsets and the JAK/STAT3 pathway in regulating cancer stemness and immune escape in esophageal squamous cell carcinoma [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 5911.