Abstract
Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype and their progression from the primary tumor setting to the metastatic setting is the critical event defining Stage IV disease, no longer considered curable. The microenvironment at brain sites is known to play a key role in influencing the ultimate fate of metastatic cells. Specifically, defects in MHC class I/II antigen processing molecules may negatively impact the clinical course and the response to T cell-based immunotherapy. In the present investigation, we analyzed the expression level of leukocyte antigen class I/II antigen processing molecules on TNBC cells (mouse: EO771, human: MDA MB231) in primary cell-line specific media and organ (brain) conditioned media to better understand their in vivo metastatic potential. TAP1 encodes a protein necessary for transport of cytosolic peptides into membrane bound organelles for MHC 1 presentation. Our western blot data showed lower level expression of MHC class I/II antigen processing molecules including Transporter associated with Antigen Processing protein 1 (TAP1) on human TNBC cells in both cell-line specific normal media and brain conditioned media. Furthermore, TNBC cells stably transfected with silencing hairpin (sh)RNA for TAP1 demonstrated a decreased susceptibility to cytotoxic T lymphocytes in in both cell-line specific media conditioned media and organ (brain) conditioned media. This data supports the functional significance of TAP expression in TNBC cells. Taken together, our data suggest that patients with low or defective TAP in TNBC cells may be at higher risk for developing brain metastases. The examination of expression of MHC class I/II and related antigen processing molecules, as critical components of the antitumor immune system, may be useful for the prediction of tumor progression and metastasis risk of triple negative breast cancer.