Abstract PS4-04-13: Murine models for triple-negative breast cancer with differential responsiveness to immunotherapy

Abstract Breast cancer is the most common cancer diagnosis in women. Clinical studies with triple-negative breast cancer (TNBC) are encouraging for immunotherapy (αPD-1) combined with chemotherapy (paclitaxel and/or carboplatin). However, additional clinical advances could be pursued more rapidly with preclinical TNBC models including syngeneic mammary tumor cell lines. Here, we generate two mammary tumor cell lines and show differential responsiveness to immunotherapy in vivo. Spontaneous mammary tumors from C57BL/6J MMTV-Cre Tp53fl/+ animals were passaged serially in cell culture and in vivo in the mammary fat pad of fully wildtype animals. The resulting lines, MM001i and MM008i, lost Trp53 and formed 1000 mm3 tumors in the mammary fat pad within 21-28 days. Despite originating from the same genetic background, MM001i and MM008i exhibit differential responses to immunotherapy. For αPD-1 immunotherapy, MM001i is poorly responsive and MM008i is strongly responsive with near-complete tumor regression. In comparison, both MM001i and MM008i respond rapidly to αCTLA-4 therapy. Both models express unique tumor antigens as evidenced by immunity to subsequent engraftment. Primary MM008i tumors exhibit greater T cell infiltration, and CD8-positive T lymphocytes are required for αPD-1 responses. These TNBC models are promising for further mechanistic studies and testing future single and combinatorial therapies. Citation Format: T. J. Kalantzakos, Y. Zhou, X. Liu, J. Proehl, C. Durfee, I. Tamayo, B. Troness, A. Soni, H. B. Gupta, R. S. Harris. Murine models for triple-negative breast cancer with differential responsiveness to immunotherapy abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-04-13.