Abstract 2701: Molecular profiling to assess the immune response to neoadjuvant SABR in early breast cancer

Abstract Radiation therapy is used successfully in the treatment of breast cancer. Stereotactic radiation therapy (SBRT) is well established in the treatment of lung cancer, brain metastases and various other metastatic sites. Localized radiotherapy can promote dendritic cells maturations and activation and enhances phagocytosis of cells by antigen-presenting cells (APCs) increased presentation of tumor-associated antigenic peptides, and T cells being primed from naïve towards memory phenotypes In this study we evaluated the ability to implement a three fraction SBRT regimen for low-risk primary carcinoma of the breast prior to lumpectomy and profiled the immune microenvironment using NanoString's GeoMx Digital Spatial Profiling (DSP) platform and we performed NanoString gene expression profiling using the Human v.1.1 PanCancer immune profiling panel. NanoString's DSP platform was used to analyze 25 patient samples from the SIGNAL 2.0 clinical trial. For analysis, region of interest were selected comparing the tumor microenvironment (TME, CD45+ve) and tumor (pan cytokeratin) in pre and post treated FFPE slides. A panel of 60-antibodies were analyzed in each region. For gene expression profiling total RNA was extracted from the frozen tissue and the human V.1.1 PanCancer Immune Profiling Panel was used. We observed notable differences in the immune microenvironment gene expression patterns in samples pre- and post-treatment. We identified a total of 175 differentially expressed genes (DEGs) using a 5% adjusted p-value across the entire patient population regardless of which radiation arm. Pathway analysis identified genes associated with activation of immune response, signaling by interleukins and adaptive immune response were significantly changed in the post treatment samples. Deconvolution of the immune cell mRNA gene expression data demonstrated that there were significant changes in the cellular composition after radiotherapy. There were significant increase in expression levels of macrophages, dendritic cells, neutrophils and CD8 T cells post radiation treatment. In conclusion we have demonstrated through proteomic and transcriptomic profiling, SBRT elicits an immune response with increases in the innate response. Citation Format: Melanie Spears, Vida Talebian, Linda Liao, Megan Hopkins, Kalan Lynn, Michael Lock, Anat Kornecki, John M. Bartlett, Muriel Brackstone. Molecular profiling to assess the immune response to neoadjuvant SABR in early breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2701.