MHC Class II Antigen Presentation Pathway and Outcome in Patients with Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) is a clinically defined subtype of invasive breast cancer that is notable for a lack of estrogen receptor, progesterone receptor and HER2 expression. As such, TNBC cannot be treated with therapeutic agents traditionally used in breast cancer that target ER and HER2 signaling. Because of limited therapeutic options and a propensity for aggressive behavior, the prognosis for TNBC is poor when compared to other breast cancer subtypes. TNBC is a heterogeneous disease and patients have disparate outcomes: while up to 42% of patients with TNBC experience rapid relapse, the remaining 58% of patients have long-term disease free survival. Clinicians currently have no way to predict which patients will benefit from standard therapy and which patients are at risk of early relapse. Chemotherapy regimens used to treat TNBC are associated with severe toxicities and side effects, and treatments are not targeted to a given patient’s tumor or individual risk profile. Therefore, there is an urgent need to develop prognostic and predictive biomarkers for the clinical management of patients with TNBC. Host immune response is an important biologic and clinical factor in breast cancer, particularly in TNBC. The presence of tumor-infiltrating lymphocytes (TILs) has been associated with improved pathologic complete response rates and diseasefree survival. In a recent publication, the Varley lab performed RNA-seq on TNBC tumor tissue and discovered an MHC Class II (MHC II) gene expression signature that is associated with significantly improved disease free survival. The overarching goal of this study is to develop and characterize a gene expression prognostic assay for patients with TNBC using NanoString technology. In addition, we plan to define expression patterns and subcellular localization of MHC II pathway components in TNBC cell lines and patient derived cancer tissue. This study will help to address an unmet clinical need for patients with TNBC through the development of a prognostic biomarker test. Furthermore, the experiments proposed here will contribute to our understanding of MHC II expression and function in breast carcinoma cells, and this will enhance our ability to apply advances in immunotherapy to patients with TNBC.