Most human breast malignancies arise in the ductal epithelium, which is colonized by a unique microbiome, yet the role of innate T lymphocytes that recognize microbial products in breast carcinogenesis is not known.  We recently characterized the major immune subsets associated with primary human breast epithelial ducts and identified for the first time the presence of Va7.2⁺ mucosal-associated invariant T (MAIT) cells.  The majority of breast-derived MAIT cells appeared Th1-biased after PMA/ionomycin stimulation, however, a substantial fraction produced IL-17A but not IFNg.  Exposure to E. coli treated breast carcinoma cell lines potently induced MAIT cell cytokine production, and also led to surface expression of LAMP-1, suggesting cytolytic degranulation.  Addition of an anti-MR1 antibody almost completely blocked MAIT cell TNFa production, and also partially blocked IFNg and degranulation, in response to bacterially treated breast carcinoma cells.  However, a portion of the MAIT cell effector responses may be mediated by expression of counter-ligands for the NKG2D receptor on breast carcinoma lines.  Thus, MAIT cells may influence breast duct carcinogenesis in multiple ways.  Their IL-17A production may ultimately play a pro-tumorigenic role; however, since it is also known to provide epithelial barrier integrity, it may hinder malignancy at earlier stages.  Moreover, MAIT cells may carry out immunosurveillance of nascently transformed cells by either T cell receptor-dependent or innate (e.g. NKG2D-mediated) pathways.  A key future question is whether imbalances within the breast duct microbiome promote cancer by influencing the functions of breast MAIT cells.