Spatial Reprogramming of Tumor Immune Microenvironments by Preoperative Radiotherapy and Immune Checkpoint Inhibition in HER2-Negative Breast Cancer
Abstract
Patients diagnosed with triple-negative breast cancer (TNBC) in the past had few options for effective treatment. More recently, the FDA approved a type of immunotherapy, referred to as anti-PD1 (aPD1) therapy, that extends the lives of patients with TNBC by stimulating the body s natural defense system. However, in these patients the current aPD1 immunotherapy is given in combination with four chemotherapy drugs, which together may cause serious side effects. In this project, we will investigate whether combining aPD1 immunotherapy with radiotherapy (RT) might allow us to eradicate metastatic disease in more breast cancer patients and improve their long-term quality of life as breast cancer survivors, while using less (or possibly eliminating the need for) chemotherapy. The major goal of this project is to identify a biomarker panel, i.e., a series of molecular changes within a patient s breast cancer, that can help us identify the breast cancer patients who are most likely to benefit from aPD1 and RT combination therapy. To achieve this goal, we will study cancer biopsy tissue from triple-negative and estrogen receptor-positive breast cancer patients taken before and after treatment with aPD1 therapy with or without RT in two clinical trials involving nearly 200 participants and representing a diverse patient population. We will analyze these samples using a cutting-edge technology called spatial transcriptomics, which will allow us to evaluate the interactions between tumor cells, immune cells, and other cell types within the breast tumor in detail and determine how these interactions changed in patients who responded to therapy. We will test the idea that uncovering the interactions between these different cell types in TNBC, and potentially also in the more common type of breast cancer that is estrogen receptor positive, will allow us to predict which patients would benefit from aPD1 combined with RT. The biomarkers identified in this project would then be used in future clinical trials to investigate whether, for some breast cancer patients, the combination of radiation and immunotherapy would be a safer and more effective alternative to the current standard of chemotherapy plus immunotherapy.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310962
Entities
People
- Simon Knott
Organizations
- Cedars-Sinai Medical Center
- United States Army