Abstract P4-03-08: Mechanisms of CD8+ T cell immunosuppression in triple negative breast cancer

Triple negative breast cancer (TNBC), defined as tumors lacking expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), are especially difficult to treat effectively. While ER+ and HER2+ breast cancer subtypes can be treated with Tamoxifen and Herceptin, respectively, there are no targeted therapies for TNBC patients. Furthermore, while only 20-30% of TNBC patients respond to chemotherapy in the neoadjuvant setting, overall outcome remains poor for non-responding patients. However, mounting evidence suggests that immune-checkpoint inhibitor immunotherapies may be especially promising for TNBC patients. We and others have shown that the presence of CD8+ T cells, a crucial component of the cytotoxic arm of the adaptive immune response, is a sign of good clinical outcome in TNBC patients. However, good outcome only correlates with CD8 +T cell invasion of the tumor parenchyma. Some patients had an accumulation of CD8+ T cells in the surrounding tumor-associated stroma, but not the tumor epithelia, and these patients responded as poorly as patients with no CD8 T cells at all. Yet how cancer associated fibroblasts (CAFs), the dominant cell type of the tumor-associated stroma, affects CD8+ T cell invasion into the tumor epithelia is still poorly understood. To identify potential stroma-dependent mechanisms which potentiate or inhibit CD8+ T cells invasion into the tumor epithelia, we performed gene expression profiling of laser-capture microdissected tumor-associated stroma (and matched epithelia) from 38 TNBC cases. Here we identify several stromal and epithelial canonical pathways as well as biomarkers that are associated with and may explain the accumulation of CD8 T cells outside of the tumor epithelia. Citation Format: Gruosso T, Gigoux M, Bertos N, Zuo D, Manem V, Monette A, Lapointe R, Haibe-Kains B, Park M. Mechanisms of CD8+ T cell immunosuppression in triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-08.