Titles and Affiliations
Professor, Medicine and Radiation Oncology
Co-Director of Breast Cancer Program
Chief, Industry Partnerships
Research area
Developing radiation-based strategies to augment anti-tumor responses in high-risk breast cancer.
Impact
Immunotherapy and chemotherapy are standard-of-care therapies in non-metastatic, triple negative breast cancer, yet 35 percent of patients do not respond to treatment. An unmet clinical need for novel and safe therapies to overcome immune-resistance and augment the effectiveness of immunotherapy exists for this group of patients. Pre-clinical studies have shown that radiation therapy has the potential to convert a non-responsive (immunogenically cold) tumor into a responsive (immunogenically hot) one. However, the optimal dose to stimulate a productive immune response had not been tested or identified in breast cancer patients. Dr. Ho and her team’s work will provide a critical step towards developing precision radiotherapy, facilitating its use in combination with immunotherapy as a successful and durable treatment approach for high-risk breast cancer patients.
Progress Thus Far
With funding from the Breast Cancer Research Foundation (BCRF), Dr. Ho and colleagues initiated and completed the P-RAD clinical trial, a multi-institutional, national phase II randomized study evaluating different radiation dose regimens in combination with immunotherapy to “prime” breast tumors for improved responses to immune checkpoint blockade and chemotherapy. The trial enrolled 104 patients with node-positive triple-negative or high-risk hormone receptor–positive breast cancer across nine institutions in the United States.
Results from the high-risk hormone receptor–positive cohort were presented at the 2025 San Antonio Breast Cancer Symposium. The findings demonstrated that the addition of radiation therapy significantly increased immune cell infiltration in tumors that lacked immune cells prior to treatment, effectively converting an “immune-cold” tumor microenvironment into an “immune-rich” state. This transition was associated with the emergence of distinct immune gene expression profiles and the formation of tertiary lymphoid structures within the tumor microenvironment.
What’s next
Dr. Ho will report clinical outcomes and biomarker analyses from the triple-negative breast cancer cohort of the P-RAD trial. In parallel, in collaboration with her scientific colleagues, spatial transcriptomic analyses will be performed on tumor and lymph node specimens from the study to characterize the composition, spatial organization, and interactions of immune cell populations within the tumor microenvironment. By mapping these cellular interactions in situ, Dr. Ho’s research aims to better understand why the combination of radiation therapy and immune checkpoint blockade produces robust anti-tumor responses in some tumors while others exhibit resistance or immune evasion. Insights from these studies will inform the development of more effective treatment strategies, including the use of pre-operative radiation to stimulate anti-tumor immunity in combination with emerging immunotherapies.
Biography
Alice Ho, MD, MBA is a Professor of Radiation Oncology and Medicine at the Houston Methodist Academic Institute and a member of the O’Neal Comprehensive Cancer Center. She serves as Co-Director of the Breast Cancer Program at Houston Methodist Hospital, Chief of Industry Partnerships, and Clinical Co-Lead of the Triple-Negative Breast Cancer Personalized Vaccine Program at the Houston Methodist Academic Institute. Dr. Ho earned her joint MD and MBA in Health Administration from Tufts University School of Medicine.
Her clinical practice is dedicated exclusively to the care of patients with breast cancer. Her research focuses on understanding how local cancer therapies can be strategically combined with biologic agents and immunotherapies to elicit systemic anti-tumor immune responses.
