Abstract 6610: Gut microbiome modulation shapes tumor responses to radiation in oral cavity carcinoma.

Abstract Tumor associated macrophages (TAMs) are key regulators in the tumor microenvironment (TME) and play an important role in the response to radiation therapy (RT). Therefore, there is a need to better understand the different factors that influence the response to RT. To this end, we used broad-spectrum antibiotics (Abx) to target the microbiome of the gut and oral cavity. We hypothesize that the gut and oral cavity microbiome are key in reshaping the TME after RT. We injected the syngeneic MOC1 cell line orthotopically into the buccal mucosa of C57BL/6 mice. Tumor-bearing mice were treated with an Abx cocktail of ampicillin, imipenem, cilastatin, and vancomycin once tumors reached a volume of 100 mm3. Tumor-bearing mice were focally irradiated (8Gy x 1) using the X-RAD SmART irradiator. At a week post RT, we magnetically isolated CD45+ leukocytes from tumors and performed high-dimensional profiling of the TME using flow cytometry and single-cell RNA sequencing (scRNA-seq). Macrophage polarization can provide insight into targetable pathways of myeloid inflammation to improve prognosis. By scRNA-seq and flow-cytometry, we found that treatment with Abx prior to RT reprograms the TME, leading to an increase in SPP1+ TAMs (P<0.05). By multiparametric flow-cytometry, we found that treatment with Abx prior to RT leads to an increase in anti-inflammatory ARG1+F4/80+ macrophages (P<0.05). The microbiome regulates the response to RT in OCSCC tumors. Strategies targeting the microbiome can have implications for better understanding the interplay between the TME and the microbiome. Citation Format: Seyedamirabbas Parizadeh, Elvin Canseco, Angelina Park, Andrew Ortega, Kit Cheung, Stephen L. Shiao, Julie K. Jang.. Gut microbiome modulation shapes tumor responses to radiation in oral cavity carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6610.