ABSTRACT
BACKGROUND: Glioblastoma (GBM) is a fatal primary brain malignancy in adults. Previous studies have shown that cytomegalovirus (CMV) is a risk factor for tumorigenesis and aggressiveness for glioblastoma. However, little is known about how CMV infection affects immune cells in the tumor microenvironment of GBM. Furthermore, there has been almost no engineered T-cell receptor (TCR)-T targeting CMV for GBM research to date. METHODS: We evaluated the CMV infection status of patients with GBM's tumor tissue by immune electron microscopy, immunofluorescence, and droplet digital PCR. We performed single-cell RNA sequencing for CMV-infected GBM to investigate the effects of CMV on the GBM immune microenvironment. CellChat was applied to analyze the interaction between cells in the GBM tumor microenvironment. Additionally, we conducted single-cell TCR/B cell receptor (BCR) sequencing and Grouping of Lymphocyte Interactions with Paratope Hotspots 2 algorithms to acquire specific CMV-TCR sequences. Genetic engineering was used to introduce CMV-TCR into primary T cells derived from patients with CMV-infected GBM. Flow cytometry was used to measure the proportion and cytotoxicity status of T cells in vitro. RESULTS: We identified two novel immune cell subpopulations in CMV-infected GBM, which were bipositive CD68+SOX2+ tumor-associated macrophages and FXYD6+ T cells. We highlighted that the interaction between bipositive TAMs or cancer cells and T cells was predominantly focused on FXYD6+ T cells rather than regulatory T cells (Tregs), whereas, FXYD6+ T cells were further identified as a group of novel immunosuppressive T cells. CMV-TCR-T cells showed significant therapeutic effects on the human-derived orthotopic GBM mice model. CONCLUSIONS: These findings provided an insight into the underlying mechanism of CMV infection promoting the GBM immunosuppression, and provided a novel potential immunotherapy strategy for patients with GBM.
Subject(s)
Cytomegalovirus , Glioblastoma , Humans , Glioblastoma/immunology , Glioblastoma/virology , Glioblastoma/pathology , Mice , Cytomegalovirus/immunology , Animals , Cytomegalovirus Infections/immunology , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Brain Neoplasms/immunology , Tumor Microenvironment/immunology , RNA-Seq , Female , Male , Single-Cell Gene Expression AnalysisABSTRACT
Road asphalt pavements cover a high percentage of urban size and contribute to heat islands. This study proposed a new method to cool asphalt pavement by incorporating a kind of hybrid mineral filler (HMF) with high emissivity into a reference asphalt mixture prepared with limestone mineral filler (LMF). The physical, emissive, solar reflective, and rheological properties of asphalt mastic and the thermal performances of asphalt mixture were covered to investigate the possibility of the proposed strategy. From Fourier transform infrared spectrum test, it can be found that HMF was physically blended with asphalt. The emissivity results show that HMF increased the emissivity of asphalt mastic from 0.9204 to 0.9820. The asphalt mastic containing HMF had similar solar reflectance with the control one. In addition, HMF could enhance the rutting resistance of asphalt mastic according to the results of multiple stress creep recovery tests. When HMF replaced LMF, the thermal conductivity of the asphalt mixture with HMF increased by 0.26 W/(m·K) (the reference value was 1.72 W/(m·K)). The combined effect of high emissivity and thermal conductivity led to a lower surface temperature (i.e., -5.4 °C) in the tests. The results of this study demonstrate that HMF is a potential material to cool asphalt pavements.
