Nodal and systemic Immune effects of radiation in HNSCC

Abstract When combined with immunotherapy, HPV-unrelated HNSCC has a high incidence of local and regional recurrence. Since nodal metastasis remains a common pattern of spread for HNSCC, elective nodal irradiation (ENI) is commonly employed to eradicate potential microscopic disease in non-involved lymph nodes. Given our developing understanding that (1) immune cells are highly radio-sensitive, and (2) that anti-tumor T cell priming, and expansion, occur in the draining lymph nodes (DLNs), we tested whether RT directed at gross tumor only could increase the effectiveness of immunotherapies. Using preclinical models and samples from canine and human trials, we tested the effects of RT with or without ENI. Immune cell differences in the tumor tissue, DLNs, and blood were characterized with flow cytometry. We found that tumor only irradiation decreased local and distant tumor growth and increased survival but increased regional recurrence. Sentinel lymph node resection or irradiation was effective at reducing regional metastasis. We show that the effectiveness of tumor only RT is likely mediated via induction of a systemic immune response dependent on antigen recognition by T cells in the DLNs. These data support the hypothesis that effective anti-tumor immunotherapy treatment requires a systemic, antigen-dependent immune response which is primed in the DLNs. Citation Format: Laurel B. Darragh, Jacob Gadwa, Keara Boss, Sana D. Karam. Nodal and systemic Immune effects of radiation in HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr IA05.