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

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-06-12 DOI:10.1038/s41467-025-60421-0

Erika Zuljan, Benjamin von der Emde, Iris Piwonski, Ana Pestana, Konrad Klinghammer, Andreas Mock, Peter Horak, Christoph Heining, Frederick Klauschen, Ina Pretzell, Melanie Boerries, Christian H. 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 T. Rieke

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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.

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巨噬细胞主导的免疫抑制微环境和晚期唾液腺癌的治疗脆弱性

唾液腺癌是一种罕见的、多样的恶性肿瘤，其特点是免疫治疗反应差。这些癌症的肿瘤免疫环境仍然知之甚少。为了解决这个问题，我们对大量晚期唾液腺癌样本的肿瘤免疫微环境进行了综合分析。大多数肿瘤表现为免疫活性低，免疫细胞浸润有限。在非腺样囊性癌组织学中，炎症与较高的肿瘤突变负荷有关。免疫检查点的亚型特异性表达在腺样囊性癌的发光样细胞中发现了VTCN1的突出表达。具有免疫抑制特性的巨噬细胞在不同亚型的免疫微环境中占主导地位。对免疫治疗的反应是有限的，并且在个别病例中与t细胞相对于巨噬细胞的比例较高有关，需要进一步研究。在这里，我们展示了唾液腺癌的免疫抑制环境，并确定了亚型特异性免疫脆弱性，可以为量身定制的治疗策略提供信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.