Abstract 399: Cyclopamine tartrate enhances antitumor immunity and suppresses triple-negative breast cancer growth.

Abstract Introduction: Triple-negative breast cancer (TNBC) remains a clinical challenge due to limited therapeutic options and poor response to immune checkpoint inhibitors (ICIs). Tumor hypoxia and abnormal vasculature contribute to an immunosuppressive microenvironment that restricts T-cell infiltration. Cyclopamine tartrate (CycT), a heme-targeting small molecule, has been shown to inhibit tumor oxidative metabolism and improve oxygenation1-2. This study examined whether CycT suppresses tumor growth and modulates the immune microenvironment in TNBC. Methods: Female BALB/c mice bearing orthotopic 4T1-Luc syngeneic tumors were treated with CycT (7.5 mg/kg Retro-Orbital Injection, twice weekly) or vehicle control. Digital calipers monitored tumor growth. Tumors were harvested for histology (H 0.001), as shown by markedly smaller resected tumors and reduced volumes over 24 days of treatment. Flow cytometric analysis demonstrated that CycT increased intratumoral CD8+ T-cell density (p 0.05) and elevated PD-1 median fluorescence intensity on CD8+ cells (p = 0.016), indicating a more active or antigen-experienced T-cell phenotype. Conclusions: These data indicate that CycT shows significant antitumor effects in a TNBC model while promoting CD8+ T-cell infiltration and activation. The results suggest that CycT reprograms the tumor microenvironment to become immune-accessible, providing a mechanistic basis for future combination strategies with immune checkpoint blockade in TNBC. References: 1. Sohoni, S. et al, Cancer Res (2019) 79 (10): 2511-2525. 2. Ghosh, P. et al., Cancer Res (2020) 80 (17): 3542-3555. Citation Format: Tianyuan Wang, Lorena Arango, Li Liu. Cyclopamine tartrate enhances antitumor immunity and suppresses triple-negative breast cancer growth abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 399.