Targeted Radiation in Combination With Immunotherapy Agents in Murine Breast Cancer Models

AACR 2020 -- Breast cancer is generally regarded as an immunologically "cold" cancer, often with minimal tumor CD8+ T cell infiltrate and low immunogenicity. In the preclinical space, there is need for robust and representative breast cancer models to test immuno-oncology (I/O) combination strategies that may convert "non-responders" (cold tumors) to "responders" (hot or warm tumors). Use of Radiation Therapy (RT) in breast cancer is known to modify the tumor microenvironment which may allow it to potentially synergize with immunotherapies. RT alone is insufficient to induce curative anti-tumor immune responses, especially in metastatic breast cancer, highlighting the need for combination I/O strategies that may boost the immune system. We have characterized the tumor immune profile of three preclinical murine breast models, 4T1-Luc, EMT6 and E0771, along with their responses to focal radiation alone and in combination with immune-modulating agents. This data provides a baseline from which future rational drug combination studies may be designed.