Abstract 6549: Immune cell-derived lymphotoxin associated with survival of patients with endometrial cancer

Background: Endometrial cancer (EC) is a prevalent gynecological malignancy, often associated with poor prognosis in advanced stages. The tumor microenvironment (TME) plays a critical role in modulating immune responses and disease progression. This study aimed to investigate the prognostic significance of lymphotoxin (LT) in EC patients. Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA) for EC were analyzed to access LT expression level, identified LT-associated gene signatures and evaluate the clinical outcomes. The cellular source of LT was determined by analyzing single-cell RNA sequencing (scRNA-seq) data from public databases. Additionally, these findings were validated in a cohort of 138 EC tissue samples from our center using quantitative PCR (qPCR) and multiplex immunofluorescence (mIF) staining. Results: Analysis of TCGA data demonstrated that EC patients with high LT expression exhibited significantly improved overall survival (OS) and disease-free survival (DFS) compared to those with low LT expression. Gene signature analysis indicated that high LT expression correlates with increased immune cell infiltration, suggesting a robust anti-tumor immune response. scRNA-seq analysis suggested that LT is predominantly expressed in T cells and B cells in EC samples when compared to normal samples. Validation in our cohort of 138 EC tissues revealed that patients with high LT expression had better OS. EC patients with high LT expression showed high expression of immune cell-related gene signatures, including Territory lymphoid structure signature, Tfh cell signature, Th1 and B cell signature and HEV signature, by qPCR. mIF staining further confirmed that increased infiltration of T cells and B cells in the TME of patients with high LT expression. Conclusion: Our findings indicate that immune cell-derived lymphotoxin serves as a potential prognostic biomarker in endometrial cancer, associated with enhanced immune cell infiltration and improved patient outcomes. These results highlight the importance of the immune microenvironment in tumor progression and support further exploration of lymphotoxin regulations in TME for identification of therapeutic target in EC. Citation Format: Tat San Lau, Jie Wu, Kit Ying Chan, Joseph Kwong, Ho Sze Lee, Chi Chiu Wang. Immune cell-derived lymphotoxin associated with survival of patients with endometrial 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 6549.