Journal Article

DKFZ-2025-01211

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A macrophage-predominant immunosuppressive microenvironment and therapeutic vulnerabilities in advanced salivary gland cancer.

Zuljan, E. ; von der Emde, B. ; Piwonski, I. ; Pestana, A.DKFZ* ; Klinghammer, K.DKFZ* ; Mock, A.DKFZ* ; Horak, P.DKFZ* ; Heining, C.DKFZ* ; Klauschen, F.DKFZ* ; Pretzell, I.DKFZ* ; Boerries, M.DKFZ* ; Brandts, C. H.DKFZ* ; Kreutzfeldt, S.DKFZ* ; Teleanu, M.-V.DKFZ* ; Hübschmann, D.DKFZ* ; Morris, L. G. T. ; Heiland, M. ; Keller, U.DKFZ* ; Conrad, T. ; Glimm, H.DKFZ* ; Fröhling, S.DKFZ* ; Ochsenreither, S.DKFZ* ; Keilholz, U.DKFZ* ; Blanc, E. ; Beule, D. ; Rieke, D.DKFZ*

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-025-60421-0

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.

Keyword(s): Humans (MeSH) ; Salivary Gland Neoplasms: immunology (MeSH) ; Salivary Gland Neoplasms: pathology (MeSH) ; Salivary Gland Neoplasms: genetics (MeSH) ; Salivary Gland Neoplasms: therapy (MeSH) ; Tumor Microenvironment: immunology (MeSH) ; Tumor Microenvironment: genetics (MeSH) ; Macrophages: immunology (MeSH) ; Immunotherapy (MeSH) ; Female (MeSH) ; Male (MeSH) ; T-Lymphocytes: immunology (MeSH) ; Carcinoma, Adenoid Cystic: immunology (MeSH) ; Carcinoma, Adenoid Cystic: pathology (MeSH) ; Carcinoma, Adenoid Cystic: genetics (MeSH) ; Salivary Glands: pathology (MeSH) ; Salivary Glands: immunology (MeSH) ; Middle Aged (MeSH)

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)
2. Translationale Medizinische Onkologie (B340)
3. DKTK HD zentral (HD01)
4. DKTK Koordinierungsstelle Dresden (DD01)
5. DKTK Koordinierungsstelle München (MU01)
6. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)
7. DKTK Koordinierungsstelle Freiburg (FR01)
8. DKTK Koordinierungsstelle Frankfurt (FM01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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