Intrinsic Molecular Characteristics of the Immune Subtypes of Salivary Mucoepidermoid Carcinoma

Background : Characterising the tumor microenvironment (TME) and immune landscape of cancer has been a promising step towards discovering new therapeutic biomarkers and guiding precision medicine; however, its application in salivary mucoepidermoid carcinoma (MEC) has been sparse. Here, we conducted a comprehensive transcriptomic study to understand the properties of the TME and immune profiles of MEC. Methods : Molecular features in heterogeneous immunophenotypic subgroups of MEC and their intrinsic characteristics were determined by applying bioinformatic and immunoinformatic analyses on 20 matched primary MEC RNA-seq data. Results : In this study, distinct two immunophenotypic subgroups, hot and cold MECs, were uncovered with their distinct molecular features, and potential immune-oncologic therapeutic options for each subgroup were suggested. In search for immunophenotype defining molecular features, tumor mutational burden, CRTC1-MAML2 fusion status, and its fusion neoantigen were not discriminable factors. However, we demonstrate that a significant inverse correlation between lipid metabolism activity and immunogenic state, and lipid metabolic regulators, such as MLXIPL and FASN , which are associated suppression of immune activity, were under-expressed in the immune-hot subgroup, contributing significant role in high immunity of immune active subgroup. Conclusions : Our study has shown heterogeneous immunophenotypic MEC subgroups with their distinctive molecular characteristics and provided potential treatment options tailored to the immune context, which yields, for the first time, new insights into TME of MEC and may help the next step to studying this uncharted cancer.