A macrophage-predominant immunosuppressive microenvironment and therapeutic vulnerabilities in advanced salivary gland cancer
Erika Zuljan, Benjamin von der Emde, Iris Piwonski, Ana Pestana, Konrad Klinghammer, Andreas Möck, Peter Horak, Christoph Heining, Frederick Klauschen, Ina Pretzell, Melanie Boerries, Christian Brandts, Simon Kreutzfeldt, Maria‐Veronica Teleanu, Daniel Hübschmann, Luc G.T. Morris, Max Heiland, Ulrich Keller, Thomas Conrad, Hanno Glimm, Stefan Fröhling, Sebastian Ochsenreither, Ulrich Keilholz, Eric Blanc, Dieter Beule, Damian Rieke
Abstract
Salivary gland cancers are rare, diverse malignancies characterized by poor response to immunotherapy. The tumor immune environment in these cancers remains poorly understood. To address this, we perform an integrative analysis of the tumor immune microenvironment in a large cohort of advanced salivary gland cancer samples. Most tumors exhibit low immune activity with limited immune cell infiltration. Inflammation is linked to higher tumor mutational burden in non-adenoid cystic carcinoma histologies. Subtype specific expression of immune checkpoints is identified with prominent expression of VTCN1 in luminal-like cells within adenoid cystic carcinoma. Macrophages with immunosuppressive properties dominate the immune microenvironment across subtypes. Responses to immunotherapy are limited and associated with a higher ratio of T-cells relative to macrophages in individual cases, warranting further investigation. Here, we show an immunosuppressive environment in salivary gland cancers and identify subtype-specific immune vulnerabilities that could inform tailored therapeutic strategies.