Sept. 29, 2026 — A research team at the University of Virginia (UVA) led by Timothy Bullock, PhD, has published results from a Focused Ultrasound Foundation-funded preclinical study examining whether targeting immunosuppressive immune cells could enhance thermally ablative focused ultrasound for the treatment of triple-negative breast cancer (TNBC). The approaches did not improve focused ultrasound–mediated tumor control, but the results revealed several biological and safety challenges that could inform future combination strategies.
Why Triple-Negative Breast Cancer Is Difficult to Treat
TNBC is an aggressive form of breast cancer that lacks three target receptors that are commonly used to treat other types of breast tumors. Without these targets, treatment options are more limited. In addition, TNBC tumors often contain large numbers of immunosuppressive myeloid cells. These cells can restrain T cells, support tumor growth, and help create a tumor microenvironment that resists immune attack.
Investigating the Role of Immune Suppression
Thermally ablative focused ultrasound uses concentrated acoustic energy to heat and destroy targeted tumor tissue. In addition to reducing the tumor directly, thermal ablation can release tumor antigens and other signals that may alert the immune system. The UVA team previously found that combining thermal focused ultrasound with the chemotherapy gemcitabine improved tumor control in a mouse model of TNBC through a T cell dependent mechanism, although the response was not durable. Because gemcitabine can affect immunosuppressive myeloid cells that restrain T cell activity, the researchers questioned whether relieving this immune suppression contributed to the improved response.
In a subsequent Foundation-funded study, the team found that although gemcitabine reduced myeloid cells in circulation, it did not reduce these cells within the tumor as anticipated. This finding prompted the researchers to explore other ways of manipulating the myeloid cells within the tumor microenvironment.
To investigate this possibility, Dr. Bullock’s team tested whether removing immunosuppressive myeloid cells or attempting to reprogram them could strengthen the immune effects of focused ultrasound. They evaluated several approaches in two mouse models of TNBC; they used chemotherapies and antibodies to reduce certain myeloid cell populations and compounds called toll-like receptor agonists, intended to stimulate or reprogram immune cells. They then combined the most promising antibody- and immune-stimulating approaches with thermally ablative focused ultrasound.
What the Researchers Found
The tested strategies changed parts of the immune environment, but none produced the durable, selective myeloid-cell changes needed to improve focused ultrasound–mediated tumor control.
The findings refine the team’s earlier work: The benefit previously observed with gemcitabine and thermal focused ultrasound may not have resulted from relieving myeloid-cell suppression. Direct effects on tumor cells or other components of the tumor microenvironment may instead contribute to the response.
This research was funded by the UVA Cancer Center, the UVA Microbiology, Immunology, and Cancer Biology Department, and the Focused Ultrasound Foundation.
October 30, 2026 
