Lynn T. Dengel, MD, MSc
Assistant Professor of Surgery
In this edition of Grand Rounds in Hematology and Oncology from March 2023, Hillary Maitland, Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, Virginia, introduces Lynn T. Dengel, MD, MSc, Assistant Professor of Surgery, Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, Virginia. In this 43-minute presentation, Dr. Dengel provides an overview of the integration of immunotherapy with surgical oncology, focusing on strategies to modulate the tumor microenvironment to enhance immune response in solid tumors. The presentation ends with a short Q&A discussion.
Dr. Dengel stresses that while immune checkpoint inhibitors have transformed the treatment landscape, many patients with advanced cancers such as melanoma continue to have limited outcomes. A key barrier is the immunosuppressive tumor microenvironment, which restricts T-cell infiltration and function.
To address this, Dr. Dengel discusses intralesional and ablative strategies designed to reprogram local immunity. She highlights the use of talimogene laherparepvec (TVEC), an oncolytic herpes virus, and CMP-001, a toll-like receptor 9 agonist, which show promising responses in combination with systemic immunotherapy. A UVA trial evaluating CMP-001 with pembrolizumab is currently enrolling.
Dr. Dengel details ablation techniques—cryoablation, radiofrequency, and focused ultrasound—to stimulate immune activity. High-intensity focused ultrasound (HIFU) is particularly interesting as it is a noninvasive modality capable of inducing immunogenic cell death and altering the tumor milieu. She outlines the AMO3 study at UVA, which examines partial tumor ablation using focused ultrasound, with or without PD-1 blockade and poly ICLC, a toll-like receptor 3 agonist.
Preclinical and pilot data suggest that focused ultrasound may increase antigen presentation, T-cell infiltration, and immunostimulatory cytokines. Ongoing and future trials, including those combining ultrasound with gemcitabine or tumor vaccines, aim to optimize treatment response. Dr. Dengel emphasizes the need for collaborative efforts to translate these insights into more durable responses, especially by targeting earlier stages of disease and exploring novel immune-priming strategies.