Research Harnesses Anti-tumor Immune Response from Radiotherapy

Using targeted radiation therapy in combination with a neutrophil stimulant was found to enhance anti-tumor immunity in a recent study published in the Proceedings of the National Academy of Science.

Radiation therapy is known as 1 of 3 core modalities in treating cancer. Studies have shown that radiation therapy targeted against a tumor can act as a “cancer vaccine” by causing neutrophil-mediated tumor cell death, which notifies the immune system to fight the cancer cells at other anatomical sites.

Radiation therapy is delivered to a primary site of cancer, resulting in the shrinkage or elimination of cancer cells in non-irradiated metastatic sites. This process is called the abscopal effect.

“The abscopal effect is only seen sporadically, but when it does happen, the effect induces a long-lasting, anti-tumor response in patients,” said senior study author Raquibul Hannan. “Our study in mice was designed to understand this phenomenon and identify strategies to enhance it.”

In the study, researchers were able to see what happens inside the tumor after radiation, and how these events kill tumor cells and lead to an anti-tumor response in the body. They found that neutrophils are key players in this radiation- induced anti-tumor immune response.

When radiotherapy is omitted, the cancer cells turn the neutrophils into tumor-associated neutrophils (TANs) to help promote cancer cell growth. When radiation therapy is present, it not only destroys TANs, but also recruits new neutrophils into the tumor.

The radiation-induced neutrophils (RT-Ns) are then able to attack tumors cells by producing molecules that can damage them. The findings further demonstrated how RT-Ns also play a key role in generating a downstream tumor-specific, T cell-mediated anti-tumor immune response.

“To our knowledge this is the first study to identify RT-Ns and to demonstrate their anti-tumor activity via both innate and adaptive immune responses,” said lead study author Tsuguhide Takeshima.

Most notably, researchers were able to find a way to enhance the tumor killing capacity of the RT-Ns through the administration of Granulocyte-colony stimulating factor (G-CSF). G-CSF is a naturally occurring cytokine that stimulates bone marrow to produce more white blood cells in the body, including neutrophils.

In a clinical setting, G-CSF is widely used to treat blood cell deficiencies in patients who are receiving chemotherapy.

“We think these are exciting finding[s] that should be easily translatable to the clinic since G-CSF is routinely used to treat neutropenia,” said study co-author Ellen Vitetta.

Researchers found that the combination of RT-Ns and G-CSFs potentiated the anti-tumor immune response, by inducing a more active neutrophil response.

“These results provide support for evaluating the combined use of radiation therapy and G-CSF in pre-clinical and clinical settings,” Hannan said. “Our long-term goal is to eliminate the sporadic nature of the abscopal effect of radiation therapy and dependable induce the response every time.”