Adenoid cystic carcinoma (ACC) is a rare and lethal cancer, with limited treatment options. We leveraged multiplex immunofluorescence to analyze the immune landscape of ACCs, identifying that ACCs are immunologically ‘cold’, with a low number of tumor-infiltrating T-lymphocytes (TILs) and very low HLA class I and B2M expression. Additional mIF analysis of normal salivary gland and normal breast tissue revealed a p63+, NFIB+, basal duct cell population with similarly low HLA/B2M class I expression patterns which may represent the cells of origin of ACC. Treatment of freshly resected ACC tissues in vitro with interferon-gamma or a STING agonist lead to strong upregulation of HLA/B2M class I expression, demonstrating the potential to pharmacologically restore HLA/B2M class I in ACC.
