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A macrophage-predominant immunosuppressive microenvironment and therapeutic vulnerabilities in advanced salivary gland cancer

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Item Type:Article
Title:A macrophage-predominant immunosuppressive microenvironment and therapeutic vulnerabilities in advanced salivary gland cancer
Creators Name:Zuljan, E., von der Emde, B., Piwonski, I., Pestana, A., Klinghammer, K., Mock, A., Horak, P., Heining, C., Klauschen, F., Pretzell, I., Boerries, M., Brandts, C.H., Kreutzfeldt, S., Teleanu, M.V., Hübschmann, D., Morris, L.G.T., Heiland, M., Keller, U., Conrad, T., Glimm, H., Fröhling, S., Ochsenreither, S., Keilholz, U., Blanc, E., Beule, D. and Rieke, D.T.
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.
Keywords:Adenoid Cystic Carcinoma, Immunotherapy, Macrophages, Salivary Gland Neoplasms, Salivary Glands, T-Lymphocytes, Tumor Microenvironment
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:16
Number:1
Page Range:5303
Date:12 June 2025
Official Publication:https://doi.org/10.1038/s41467-025-60421-0
PubMed:View item in PubMed

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