salivary duct carcinoma genomics

Salivary duct carcinoma is a rare and aggressive salivary gland cancer subtype with poor prognosis. Its mutational landscape has been described rather exhaustively but little is known regarding its functional genomics and tumor microenvironment. In this study, we combined transcriptomics and proteomics to obtain a first characterization of deregulated pathways, which revealed the importance of Notch, TGB-β, and interferon-γ signaling. We then associated computational biology, immunohistochemistry, multiplexed immunofluorescence, and digital imaging to start charting the cellular network within the microenvironment, identify two well-defined groups of tumors according to their immune infiltrate, find novel SDC immune checkpoints, and show the role macrophages and NK cells in immunosuppression. Furthermore, we showed a clear trend between recurrence free survival and M2 macrophage abundance, and, independently, α-SMA abundance – a measure of desmoplastic stromal reaction. Altogether, these many findings open new perspectives for SDC. Classical patient stratification according to the immune infiltrate should be applied before choosing an immunotherapy. The microenvironment offers new actionable targets such as macrophages or NK cells, or even fibroblasts or hyaluronic acid in the absence of immune infiltrate. Related therapies are developed e.g. against pancreatic tumors that could inspire equivalents for SDC. Combinations with drugs targeting SDC mutated genes might also contribute to patient-specific regimens.