Abstract 2833: Exploring the impact of IL-17 pathway modification on radiation dermatitis and radiation therapy efficacy

Abstract Here we explore the role of Interleukin-17 (IL-17) in the promotion of radiation dermatitis (RD) and radiation therapy (RT) efficacy. RD is a common and potentially treatment-limiting skin toxicity that occurs following RT. When the treated tumor is close to the skin, as in head and neck or breast cancer, RD is the most common acute adverse event which negatively impacts patients’ quality of life; however, evidence-based treatments are limited. We performed RNA sequencing of RT-treated skin in both human skin and a murine model, which each showed increased expression of IL-17 Receptor type C (IL-17RC). To further explore the role of the IL-17 pathway in the development of RD, both genetic knockout of IL-17RC and pharmacologic blocking of IL-17A in mouse models were studied, and both were found to have attenuated histopathological signs of RD, including inflammation, acanthosis, and fibrosis when compared to controls. After establishing the importance of the IL-17 pathway on RD, we explored the impact of such IL-17 pathway modification on the anti-tumorigenic efficacy of RT, an important step when considering a future IL-17 neutralizing therapy for RD. A Trans-PyMT murine model of triple-negative breast cancer was used to evaluate the impact of IL-17A neutralization on RT efficacy. There was no difference found in the efficacy of RT in mice treated with IL-17A neutralizing antibody as compared with saline control. Overall, we present a clinically relevant murine model which advances our understanding of the immunopathogenesis of RD and suggests further exploration of targeted therapies for RD prophylaxis is warranted. Additionally, we show that modifying the IL-17 pathway is effective in mitigating RD phenotype with no impact on RT efficacy. Citation Format: Megan E. Pirtle, Yana Kost, Alana Deutsch, Kosaku Shinoda, Beth N. McLellan. Exploring the impact of IL-17 pathway modification on radiation dermatitis and radiation therapy efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2833.