A new study published in JCI Insight researchers showed that combining high-intensity focused ultrasound with two immunotherapies (a PD-1 checkpoint inhibitor and TLR9 agonist) can produce excellent response rates in mouse models of epithelial cancer and that the immunotherapies must come first for it to be effective.  Researchers sais “These combination protocols can achieve a complete response in a large fraction of solid tumors” We found that we could achieve responsea in distant leisions, but the specific protocol is really important.”

They said high-intensity focused ultrasound is a relatively new approach to destroying or reducing malignant tumors tumor in which the ultrasonic beam heats tumor tissue and kills the cancer cells in minutes. But the effect is localized abd the researchers hoped that by combining it with immunotherapy they could treat more systemically. In immunotherapy ,  the PD-1 inhibitor takes the brakes off  cytotoxic T-cells, releasing them to fight cancer with greater intensity.  The TLR9 agonist boosts dendrite cells and other immune components.

The researchers were relying on the abscopal effect of the ultrasound like observed in radiation theraoy patients. As cancer cells die, they release antigens that kick up the immune response, focusing T cells on the tumor and turning a local effect into a systemic one. Ultrasound also contributes by shrinking the tumor, making it more vulnerable to immune attack.

In their study, researchers tested the immunotherapy both before and after ultrasound to determine the more effective protocol. The found that immunotherapy before the ultrasound was the best approach and lead to a complete response in 80% of the mice after 90 days,. They said the study showed that early immunotherapy both expanded the T-cell population and primed them to respond-like a swarm of angry bees waiting for a target. “You get the immune response going and then you deliver the focal therapy.”  Thus, treating multiple tumor sites sequentially with ultrasound following immunotherapy was more effective than immunotherapy alone.  Researchers concluded “We know we need to personalize theres therapues and Were develoiping the tools that will help us do that.”