Characterization Of The Immune Infiltrate In Her2+Breast Cancer

A subset of HER2+ breast cancer is characterized by high expression of lymphocyte-associated genes and the presence of a robust, histologically apparent, lymphocytic infiltrate. The presence of an immune signature and lymphocytic infiltration is associated with improved outcome, and may be a marker of improved response to trastuzumab-based therapy. The relationship of the immune signature in these cancers to the biology and functional status of the lymphocyte subsets present in the tumor microenvironment remain unclear. To better characterize the immune microenvironment of HER2+ cancers, we have analyzed paired RNA sequencing data and histologic image data from The Cancer Genome Atlas. We have confirmed the presence of a strong immune signature in a subset of HER2+ breast cancers that is correlated with the presence of a robust lymphocytic infiltrate. Immuno-phenotyping of the lymphocytic infiltrate was performed on an independent set of HER2+ breast cancers from the Rutgers Cancer Institute of New Jersey. CD8+ T-cells and macrophages are a significant component of the immune infiltrate in these cancers. Interestingly, CD20+ B-cells were also present in the tumor stroma as large aggregates whose organization is suggestive of the presence of ectopic germinal centers. The relationship of lymphocyte subsets present in HER2+ breast cancer, immunoglobulin subtypes expressed and correlation with immune checkpoint protein expression will be presented. The composition of the immune infiltrate and its organization into ectopic germinal centers may give new insight into the role of the immune microenvironment in the development of HER2+ breast cancer and the response to trastuzumab. Citation Format: Shridar Ganesan, Gabriela Alexe, Kim M Hirshfield, Ming Yao, Gyan Bhanot, Toppmeyer Deborah. Characterization of the immune infiltrate in HER2+ breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-04-10.