Dr. Larner on Integrating Radiation Therapy With Immune Checkpoint Blockade in NSCLC

James Larner, MD, professor and chair of Radiation Oncology, University of Virginia Health System, discusses integrating radiation therapy with immune checkpoint blockade in patients with non—small cell lung cancer (NSCLC).

Radiation has tremendous potential in stimulating the immune system, explains Larner. Radiation increases antigen presentation and dendritic cell activity through the damage associated molecular pattern with the release of ATP, calreticulin, high mobility group proteins, and so forth. This results in the so called abscopal effect, says Larner.

However, there is a lot that is unknown about how to integrate radiation with immune checkpoint blockade, such as which comes first and the optimal therapeutic dose. Recently, several molecular pathways have been identified, including the cGAS-STING pathway, where damaged DNA goes into the cytosol and turns on an interferon response that leads to dendritic cell stimulation. Determining the optimal dose is important, explains Larner, because if too high or too low of a dose is given, there may not be a response.

The real future lies in understanding the potential permutations and pathways that are involved in potentiating the immune response and whether radiation can aid in enabling a systemic effect, states Larner.