A macrophage-predominant immunosuppressive microenvironment and therapeutic vulnerabilities in advanced salivary gland cancer Journal Article
| Authors: | 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.; Rieke, D. T. |
| Article Title: | A macrophage-predominant immunosuppressive microenvironment and therapeutic vulnerabilities in advanced salivary gland cancer |
| 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. © The Author(s) 2025. |
| Keywords: | adult; controlled study; aged; middle aged; major clinical study; gene deletion; genetics; histopathology; advanced cancer; t lymphocyte; t-lymphocytes; cancer immunotherapy; immune system; gene expression; basal cell carcinoma; cell infiltration; cohort analysis; pathology; immunoreactivity; histology; chromosome aberration; immunology; immune response; immunotherapy; salivary gland; salivary gland tumor; salivary gland neoplasms; salivary glands; salivary gland cancer; adenoid cystic carcinoma; tumor; macrophage; phagocytosis; macrophages; immunosuppressive treatment; carcinoma, adenoid cystic; therapy; immunocompetent cell; transcriptome sequencing; tumor microenvironment; tumor-associated macrophage; salivary duct carcinoma; carcinoma ex pleomorphic adenoma; cyclin dependent kinase 2 inhibitor; vulnerability; mucoepidermoid tumor; cell component; cancer; humans; human; male; female; article; whole genome sequencing; rna sequencing; hierarchical clustering; whole exome sequencing; tumor mutational burden; multiomics; m2 macrophage |
| Journal Title: | Nature Communications |
| Volume: | 16 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2025-06-12 |
| Start Page: | 5303 |
| Language: | English |
| DOI: | 10.1038/s41467-025-60421-0 |
| PUBMED: | 40506428 |
| PROVIDER: | scopus |
| PMCID: | PMC12162891 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
