Timing of radiation and immunotherapy may make all the difference in head and neck cancers

This figure illustrates how lymph nodes (green bean object in drawing) connects to tumors, while the right side gives a cellular-level view of immune cells (stained red) traveling through lymphatic channels between lymph nodes and tumors. Sparing the lymph node during radiation allows increased flow of immune cells to the lypmh node. Photo Credit: Saddawi-Konefka et al./ Nature Communications

CANCER DIGEST – Aug. 10, 2025 – Researchers have shown in mice that precisely timing radiation therapy and immunotherapy can potentially improve treatment outcomes in cancer of the neck, mouth and nose. The study results are published in the July 28, 2028 journal Nature Communications.

Based on their findings, the researchers are launching clinical trials at Providence Earle Chiles Cancer Center in Portland, OR,  to test the timing strategy in humans.

Head and neck cancers are diagnosed in about 890,000 people each year with nearly 450,000 deaths. Treatments are limited with surgery, radiotherapy and chemotherapy being the principal strategies. While having limited effectiveness they also result in significant side effects and disfigurement.

More recently, however, immunotherapy has emerged as a new standard of care for recurrent/metastatic head and neck cancers, improving overall survival and long-term control for a minority of patients. 

Looking to expand the effectiveness of the treatment to more patients, Robert Saddawi-Konefka, M.D., Ph.D at the University of California San Diego, led a team of researchers investigating the interaction between lymph nodes connected to the cancerous tumors.

They found in mice that using lymph node-sparing radiation therapy before delivering immunotherapy resulted in a complete and durable tumor response, meaning the tumor was eliminated and did not regrow in 15 of 20 mice treated this way.

When they analyzed the result, the researchers found that the timing strategy amplified the migration of a specific type of immune cell, called activated CCR7+ dendritic cells, which are cells that migrate from peripheral tissue to lymph nodes where they interact with T cells to initiate an immune response. It appears that not damaging the lymph nodes with radiation boosted the migration of these CCR7+ dendritic cells and triggered a stronger immune response.

The finding has implications for delivery of immunotherapy following radiation therapy in a number of other cancers as well as head and neck cancers. The researchers caution that it will take further research to determine the full potential of timed treatment following lymph node-sparing radiation. 

Nevertheless, because it is relatively safe adjustment to an already approved treatment protocol for these cancers, the researchers have launched a clinical trial in collaboration with clinical researchers at Providence Earle Chiles Cancer Center in Portland, OR.