Immunotherapy has been an exciting development to treat various cancers. Unfortunately, it is not that effective in patients with hepatocellular carcinoma (HCC) because of the high rates of cirrhosis. But a research team at the University of Texas MD Anderson Cancer Center in Houston has developed a new technique that may improve the effectiveness of immunotherapy in HCC.
The findings of abstract No. 331, “Immune modulation by molecularly targeted photothermal ablation in a mouse model of advanced hepatocellular carcinoma and cirrhosis,” will be presented Wednesday at 3 p.m. as part of Scientific Session 34, IO Frontiers 2.
Swathi Pavuluri, a rising third-year medical student at Rutgers New Jersey Medical School, was able to take part in the research as a 2021 Society of Interventional Radiology Summer Medical Intern. She joined the MD Anderson lab of interventional radiologist Rahul A. Sheth, MD, last summer—an experience that increased her desire to become an interventional oncologist.
When Ms. Pavuluri arrived, Dr. Sheth’s lab had already developed a molecularly targeted photothermal ablation (MTPA) technique that provides thermally tunable, tumor-specific heat generation.
The study Ms. Pavuluri is presenting evaluates the morphologic and immunologic effects of MTPA in an immunotherapy-resistant syngeneic mouse model of HCC in a background of toxin-induced cirrhosis.
“This is commonly an issue that happens with people, where if they have HCC, they can also have cirrhosis, and cirrhosis typically makes the tumor microenvironment much more resistant to immunotherapy,” Ms. Pavuluri explained.
Immunotherapy uses antibodies called immune checkpoint inhibitors to stop the process that normally prevents immune cells from attacking cancer cells. In this study, researchers aimed to prevent the PD-1 protein from stopping the immune system’s attack on cancer.
Twelve cirrhotic mice with orthotopic tumors were randomized in each arm of the study to receive systemic anti-PD-1 therapy plus sham surgery, anti-PD-1 therapy plus MTPA, MTPA alone, or sham surgery. MTPA was performed by first administering to the mice indocyanine green (ICG), a fluorescent dye. Next, tumor-specific hyperthermia was generated with a near-infrared laser. The target thermal dose was 42–45°C for five minutes to stimulate tumor immunity rather than lethal hyperthermia for ablation. Harvested tissue was analyzed with immunohistochemistry, flow cytometry, bulk RNA sequencing and single cell RNA sequencing.
The results showed that “there were much higher levels of cytotoxic T cell infiltration with our therapy alone and with our therapy combined with anti-PD1, which is an immune checkpoint inhibitor, than compared to just control or just anti-PD1 alone,” Ms. Pavuluri said. “We also found that levels of regulatory T cells, which normally keep these T cells in check, were lower, which is a good thing because it allows for more cytotoxic T cells to infiltrate the tumor.”
This new technique shows how interventional radiology can “more precisely target tumors and selectively bind to tumors rather than other tissues in the body. That’s a really exciting innovation going forward,” Ms. Pavuluri said.
