Lineage and spatial mapping of glioblastoma-associated immunity

The diversity of molecular states and cellular plasticity of immune cells within the glioblastoma environment remain poorly investigated. Here, we performed scRNA-sequencing of the immune compartment, mapping potential cellular interactions that lead to the exhausted phenotype of T cells. We identified Interleukin 10 response during T cell activation leading to the exhausted state. By use of an in-silico model, we explored cell-cell interactions and identified a subset of myeloid cells defined by high expression of HMOX1 driving T cell exhaustion.

We showed a spatial correlation between T cell exhaustion and mesenchymal-like gene expression, co-located with HMOX1 expressing myeloid cells. Using human neocortical sections with myeloid cell depletion, we confirmed the functional interaction of myeloid and lymphoid cells, leading to the exhausted state of T cells. A comprehensive understanding of cellular states and plasticity of lymphoid cells in GBM aids in providing successful immunotherapeutic approaches.