Tumor-associated macrophages in meningiomas: a novel biomarker for poor survival outperforming the benefits of T cells

作者：Catharina Lotsch, Rolf Warta, Fang Liu, Gerhard Jungwirth, Carmen Rommel, Mandy Barthel, Katrin Lamszus, Almuth Friederike Kessler, Niels Grabe, Mario Loehr, Ralf Ketter, Christian Senft, Sybren L. N. Maas, Philipp Sievers, Manfred Westphal, Sandro Manuel Krieg, Andreas Wilhelm Unterberg, Matthias Simon, Andreas von Deimling, Felix Sahm, David Ronan Raleigh, Christel C. Herold‐Mende · 发表于：Acta Neuropathologica · 年份：2025 · DOI：10.1007/s00401-025-02948-6 · 被引用次数：7 · 研究领域：Glioma Diagnosis and Treatment、Brain Metastases and Treatment、Meningioma and schwannoma management

Tumor-associated macrophages (TAMs) represent the main immune cell population in various brain malignancies, but there is rare knowledge on the functional and, in particular, the prognostic role of TAMs in the meningioma (MGM) microenvironment. Here, we investigated TAM frequencies, activation state, survival-associated changes, and their association with tumor-infiltrating T lymphocytes (TILs) in two independent study samples comprising altogether 680 MGMs. To this end, we performed tissue cytometry analyses, quantified tissue cytokine levels, and integrated previously published TIL infiltration and microarray datasets in the discovery cohort comprising n = 195 clinically well-annotated cases. This was complemented by a DNA methylation-based deconvolution approach to predict TAM and TIL infiltration rates using immune cell-specific CpG sites as well as survival associations in an independent validation cohort of n = 485 MGMs. Our findings revealed substantial but heterogeneous TAM infiltration in newly diagnosed MGMs, with increased numbers of pro-tumoral TAMs in clinically aggressive tumors. Additional cytokine and transcriptome analyses corroborated the presence of an immunosuppressive niche in TAM-enriched MGMs. Importantly, a high frequency of pro-tumoral TAMs was associated with poor patient outcome, and high TAM infiltration was further identified as an independent prognostic factor for inferior survival, counteracting the beneficial prognostic effect of TILs. Moreover...