Abstract 5163: Characterization of endometrial cancer xenograft humanized mouse models

Abstract Background: Recently, immunotherapy with immune checkpoint inhibitors (ICIs) has shown promising efficacy in endometrial cancer (EC), particularly in patients with mismatch repair deficiency (dMMR). Preclinical models of EC are essential for evaluating the efficacy of immuno-oncology (IO) drugs and investigating strategies to enhance the antitumor responses to immunotherapy. Humanized (Hu) mouse models can contribute to a better understanding of the underlying mechanisms associated with the improved efficacy of ICIs in treating patients with EC. Methods: We established EC xenograft Hu-mouse models by subcutaneously transplanting dMMR HEC-1A and Ishikawa human EC cells into CD34+ Hu-mice. Tumor growth was monitored by periodic measurements with a caliper. The immunophenotypical characterization of EC xenografts in Hu-mice was performed using immunohistochemical staining and flow cytometry analysis. Results: Tumor development and growth were observed in both EC cell lines within CD34+ Hu-mice. In the Hec-1A xenograft Hu-mouse model, tumor growth was significantly inhibited compared to the immunodeficient mouse model. Flow cytometry analysis of tumors, spleen, and blood from Hu-mice injected with HEC-1A cells revealed a high frequency of human immune cells, exhibiting various subtypes, including CD4+/CD8+ T cells, NK cells, NKT cells, B cells, and myeloid cells. In contrast, no significant difference in tumor growth was observed for Ishikawa xenografts between Hu- and the immunodeficient mouse model. While the spleen and blood of Hu-mice harboring Ishikawa tumors exhibited a high frequency of human immune cells similar to the HEC-1A model, the xenografts demonstrated an immune-desert phenotype, characterized by a low frequency of tumor-infiltrating immune cells. Notably, both HEC-1A and Ishikawa EC xenografts in Hu-mice exhibited a significantly higher proportion of PD-1/PD-L1+ T and B cells compared to those found in the spleen and blood. Conclusion: Two models of EC xenograft were successfully established in Hu-mice, demonstrating contrasting tumor immune phenotypes. These models might serve as valuable tools for evaluating the efficacy of immunotherapy in EC. Citation Format: Sung Wan Kang, Ji-Young Lee, Min-Seo Lee, Ok-Ju Kang, Yong-Man Kim, Chong Jai Kim, Shin-Wha Lee. Characterization of endometrial cancer xenograft humanized mouse models [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 5163.