Search

Summary: tRNA-derived ncRNAs are a heterogeneous class of non-coding RNAs recently proposed to be active regulators of gene expression and be involved in many diseases, including cancer. Consequently, several online resources on tRNA-derived ncRNAs have been released. Although interesting, such resources present only basic features and do not adequately exploit the wealth of knowledge available about tRNA-derived ncRNAs. Therefore, we introduce tRFUniverse, a novel online resource for the analysis of tRNA-derived ncRNAs in human cancer. tRFUniverse presents an extensive collection of classes of tRNA-derived ncRNAs analyzed across all the TCGA and TARGET tumor cohorts, NCI-60 cell lines, and biological fluids. Moreover, public AGO CLASH/CLIP-Seq data were analyzed to identify the molecular interactions between tRNA-derived ncRNAs and other transcripts. Importantly, tRFUniverse combines in a single resource a comprehensive set of features that we believe may be helpful to investigate the involvement of tRNA-derived ncRNAs in cancer biology.

Summary: Gliomas are one of the leading causes of cancer-related death in the adolescent and young adult (AYA) population. Two-thirds of AYA glioma patients are affected by low-grade gliomas (LGGs), but there are no specific treatments. Malignant progression is supported by the immunosuppressive stromal component of the tumor microenvironment (TME) exacerbated by M2 macrophages and a paucity of cytotoxic T cells. A single intravenous dose of engineered bone-marrow-derived myeloid cells that release interleukin-2 (GEMys-IL2) was used to treat mice with LGGs. Our results demonstrate that GEMys-IL2 crossed the blood-brain barrier, infiltrated the TME, and reprogrammed the immune cell composition and transcriptome. Moreover, GEMys-IL2 extended survival in an LGG immunocompetent mouse model. Here, we report the efficacy of an in vivo approach that demonstrates the potential for a cell-mediated innate immunotherapy designed to enhance the recruitment of activated effector T and natural killer cells within the glioma TME.

Summary: Recent studies have shown the importance of the dynamic tumor microenvironment (TME) in high-grade gliomas (HGGs). In particular, myeloid cells are known to mediate immunosuppression in glioma; however, it is still unclear if myeloid cells play a role in low-grade glioma (LGG) malignant progression. Here, we investigate the cellular heterogeneity of the TME using single-cell RNA sequencing in a murine glioma model that recapitulates the malignant progression of LGG to HGG. LGGs show increased infiltrating CD4+ and CD8+ T cells and natural killer (NK) cells in the TME, whereas HGGs abrogate this infiltration. Our study identifies distinct macrophage clusters in the TME that show an immune-activated phenotype in LGG but then evolve to an immunosuppressive state in HGG. We identify CD74 and macrophage migration inhibition factor (MIF) as potential targets for these distinct macrophage populations. Targeting these intra-tumoral macrophages in the LGG stage may attenuate their immunosuppressive properties and impair malignant progression.