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Glioblastomas (GBM) are incurable central nervous system (CNS) cancers characterized by substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutic targets identified in peripheral non-CNS cancers are applicable to GBM requires further study. Here, we identify that the critical immunosuppressive target in peripheral cancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotective in GBM. Genetic or pharmacological TREM2 deficiency promotes GBM progression in vivo. Single-cell and spatial sequencing reveals downregulated TREM2 in GBM-infiltrated myeloid cells. TREM2 negatively correlates with immunosuppressive myeloid and T cell exhaustion signatures in GBM. We further demonstrate that during GBM progression, CNS-enriched sphingolipids bind TREM2 on myeloid cells and elicit antitumor responses. Clinically, high TREM2 expression in myeloid cells correlates with better survival in GBM. Adeno-associated virus-mediated TREM2 overexpression impedes GBM progression and synergizes with anti-PD-1 therapy. Our results reveal distinct functions of TREM2 in CNS cancers and support organ-specific myeloid cell remodeling in cancer immunotherapy. [Display omitted] • TREM2 deficiency promotes tumor progression in murine glioblastoma (GBM) models • TREM2 downregulation is observed in individual GBM-infiltrated myeloid cells • AAV-mediated TREM2 overexpression represses GBM growth and synergizes with ICB • Lipidic damage signals causes a TREM2-mediated protective response in CNS cancers Zhong et al. show that TREM2 plays an immunoprotective role prompted by central nervous system-enriched sphingolipids during glioblastoma (GBM) progression. Single-cell and spatial sequencing revealed TREM2 downregulation in GBM-infiltrating myeloid cells. TREM2 overexpression represses GBM and synergizes with anti-PD-1 therapy. This study highlights organ-specific remodeling of myeloid cell targets in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Background: As a widely used toxic traditional herbal medicine, the quality of the Fructus Xanthii must be well controlled to ensure the clinical therapeutic efficacy and safety.Aims: A rapid, and sensitive using ultra-high performance liquid chromatography to triple quadrupole tandem mass spectrometry (UPLC-MS/MS) in selected reaction monitoring (SRM) mode was developed and validated for simultaneous quantitation of determination active and toxic ingredients form processed by stir-frying and raw materials of Fructus Xanthii.Methods: Chromatographic separation of all targeted compound was performed on Waters ACQUITY UPLC HSS T3 column (50 mm × 2.1 mm, 1.8 μm). Moreover, the method was successfully applied in thirty-six samples of Fructus Xanthii collected from different sources in China. The processing method was optimized through Box-Behnken statistical design and response surface methodology.Results: In this work, chemometrics was able to successfully discriminate and classify among samples. The optimal incubation conditions were as follows: under heating in a pot at 295 °C, medicine at 120 °C for 11.0 min with flipping frequently.Conclusions: Therefore, the established UPLC-QQQ-MS method in combination with chemometric analysis provides a rapid, flexible and reliable method for quality assessment of Fructus Xanthii. Importantly, the optimized experimental value of the processing process provides the basis for future research. [ABSTRACT FROM AUTHOR]