Research Shows Radiotherapy Dampens Immune Response

A new study shows that while radiotherapy (RT) elicits an immune response that kills tumor cells, it also boosts immunosuppressive cells, which dampen the anti-tumor immunity.

University of Rochester Medical Center (URMC, NY, USA) researchers conducted a study that used a murine model in which syngeneic tumor cell lines were grown intramuscularly and treated with local RT; they then assessed the effects of RT on the systemic and intratumoral immune response. They found that RT stimulated increased production of two chemokines, CCL2 and CCL5, at the tumor site, which lead to increased CCR2+ CCR5+ monocytes in circulation.

This response subsequently altered the composition of the intratumoral immune infiltrate, favoring the largely immunosuppressive CCR2+ CCR5+ monocytes. Importantly, the researchers showed that a CCR2/CCR5 antagonist administered daily, starting two days prior to RT, reduced both circulating and intratumoral monocytes, resulting in increased efficacy of RT in radio-responsive tumors. They therefore suggest that immunotherapy two days prior to RT could hold significant benefits for many different types of cancer. The study was published on November 11, 2016, in Oncotarget.

“Scientists already know that radiotherapy stimulates anti-tumor cells and helps to control cancer's growth. What is less understood is why radiotherapy cannot cure cancer,” said lead author Scott Gerber, PhD, an assistant professor in the URMC department of surgery. “Our observations of what happens during radiotherapy when cells are recruited to the tumor site and surrounding tissue has intriguing implications for how to improve treatment.”

RT increases the circulation of monocytes, which compose 2-10% of all leukocytes in the human body and serve multiple roles in immune function, including replenishing resident macrophages under normal conditions; migration within approximately 8–12 hours in response to inflammation signals from sites of infection in the tissues; and differentiation into macrophages or dendritic cells to effect an immune response. In many patients, the circulating level of monocytes is already high prior to cancer treatment, and sometimes can indicate poor prognosis.

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