- Researchers at Stanford University are investigating solid tumor microenvironment response to focused ultrasound ablation combined with cancer immunotherapies.
- The combination treatment induced distinct responses in each of the two models.
- The Foundation- and NIH-funded preclinical study was conducted in models of breast and pancreatic cancer.
Multiomic Analysis for Optimization of Combined Focal and Immunotherapy Protocols in Murine Pancreatic Cancer
Dr. Katherine Ferrara’s research team at Stanford University is working to determine how different solid tumor microenvironments respond to focused ultrasound ablation combined with cancer immunotherapies. They recently completed a Foundation- and NIH-funded study in which they developed complex protocols and conducted experiments in two different preclinical models: one for breast cancer and one for pancreatic cancer. Several of the new discoveries may make a large impact in the field.
Effects in Both Models
During the comprehensive study, which spanned several years, the group found that the combination of focused ultrasound ablation plus cancer immunotherapeutics created effects in both models, but in different ways. For the model of pancreatic cancer, the treatment enriched immune cell migration pathways; in the breast cancer model, the treatment extensively enriched wound healing pathways. Dendritic cells were activated in both models.
Dr. Ferrara and her team chose to study these models because they have tumor features similar to human metastatic cancers. For example, the pancreatic tumor model has a dense stroma and sparse tumor cell distribution. The breast cancer model is Her-2-positive and has a dense tumor cell distribution and larger number of immune cells. These factors will hopefully make the research more readily translatable to future clinical trials.
Exciting Pancreatic Cancer Findings
The paper states, “…the ultimate goal is to ablate a local region while inducing an anti-tumor immune response to treat the systemic disease.” Toward this goal, the team found especially exciting results in the model of pancreatic cancer. Beyond impacting the pathways for cell migration and activating dendritic cells, focused ultrasound ablation plus immunotherapy also activated desirable immune cells (natural killer cells and T cells) in distant (metastatic) tumors and changed the tumor microenvironment in a way that could allow the immune system to more effectively attack tumors. The researchers confirmed these outcomes by observing that the treatment significantly extended survival in the treated group.
“We found significant differences in how focused ultrasound ablation plus immunotherapeutics impacted both models,” said first author Dr. James Wang. “Most importantly, our results demonstrated the benefit of combining focused ultrasound with immunotherapy for pancreatic cancer, where the combined treatment increased survival over immunotherapy alone.”
Breast Tumor Differences
Unlike pancreatic cancer’s sparse tumor cell distribution, the Her-2-positive breast cancer model has a dense tumor cell distribution with many immune cells. These varying tumor microenvironments have specific inflammatory effects that must be considered when incorporating focused ultrasound ablation into breast cancer treatment protocols.
Those who are interested in learning more about the study methods should read the full text of the paper, which is available via open-access. The group used single-cell sequencing, spectral flow cytometry, histological analyses, gene ontology analysis, and spectral and digital cytometry to assess immune system responses to focused ultrasound ablation plus immunotherapy.
This study was partially funded by the Foundation along with multiple NIH grants.
Immunotherapy Plus Focused Ultrasound Shrinks Tumors April 2017
Investigator Profile: Kathy Ferrara, PhD April 2017