TY  - JOUR
AU  - Zuljan, Erika
AU  - von der Emde, Benjamin
AU  - Piwonski, Iris
AU  - Pestana, Ana
AU  - Klinghammer, Konrad
AU  - Mock, Andreas
AU  - Horak, Peter
AU  - Heining, Christoph
AU  - Klauschen, Frederick
AU  - Pretzell, Ina
AU  - Boerries, Melanie
AU  - Brandts, Christian H
AU  - Kreutzfeldt, Simon
AU  - Teleanu, Maria-Veronica
AU  - Hübschmann, Daniel
AU  - Morris, Luc G T
AU  - Heiland, Max
AU  - Keller, Ulrich
AU  - Conrad, Thomas
AU  - Glimm, Hanno
AU  - Fröhling, Stefan
AU  - Ochsenreither, Sebastian
AU  - Keilholz, Ulrich
AU  - Blanc, Eric
AU  - Beule, Dieter
AU  - Rieke, Damian
TI  - A macrophage-predominant immunosuppressive microenvironment and therapeutic vulnerabilities in advanced salivary gland cancer.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01211
SP  - 5303
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Salivary Gland Neoplasms: immunology
KW  - Salivary Gland Neoplasms: pathology
KW  - Salivary Gland Neoplasms: genetics
KW  - Salivary Gland Neoplasms: therapy
KW  - Tumor Microenvironment: immunology
KW  - Tumor Microenvironment: genetics
KW  - Macrophages: immunology
KW  - Immunotherapy
KW  - Female
KW  - Male
KW  - T-Lymphocytes: immunology
KW  - Carcinoma, Adenoid Cystic: immunology
KW  - Carcinoma, Adenoid Cystic: pathology
KW  - Carcinoma, Adenoid Cystic: genetics
KW  - Salivary Glands: pathology
KW  - Salivary Glands: immunology
KW  - Middle Aged
LB  - PUB:(DE-HGF)16
C6  - pmid:40506428
DO  - DOI:10.1038/s41467-025-60421-0
UR  - https://inrepo02.dkfz.de/record/302013
ER  -