2716 - Targeting Commensal Bacteria Reprograms the Tumor Microenvironment after Radiation Therapy in a Murine Oral Cavity Tumor Model
Presenter(s)
E. Canseco1, A. Park2, K. Cheung3, C. McWilliam3, A. Ortega3, I. Vazquez3, H. Xiao3, K. Asadipour3, T. B. Dar1, A. T. Nguyen4, S. L. Shiao5, and J. K. Jang1; 1Cedars-Sinai Medical Center, Los Angeles, CA, 2UCLA, West Hollywood, CA, 3Cedars-Sinai Medical Center, West Hollywood, CA, 4Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, 5Cedars Sinai Medical Center, Los Angeles, CA
Purpose/Objective(s): Tumor associated macrophages (TAMs) are key regulators in the tumor microenvironment (TME) and play an important role in the response to radiation therapy (RT). As innate immune cells, they respond to shifts in the microbiome. In other types of cancers, the bacterial microbiome has been shown to alter the response to radiation therapy. In an oral cavity squamous cell carcinoma mouse model, we used broad spectrum antibiotics (abx) to deplete bacteria in the gut and oral cavity to study how bacterial changes reshape the tumor microenvironment after radiation therapy.
Materials/Methods: 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, followed by focal irradiation (8Gy x 1) to tumors using the X-RAD SmART irradiator. At a week post RT, we isolated CD45+ leukocytes from tumors and performed high-dimensional profiling of the TME using flow cytometry and single-cell RNA sequencing (scRNA-seq).
Results: 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).
Conclusion: 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.