Non-inflammatory tumor microenvironment of diffuse intrinsic pontine glioma.

摘要: Diffuse intrinsic pontine glioma (DIPG) is a universally fatal malignancy of the childhood central nervous system, with median overall survival 9–11 months. We have previously shown that primary DIPG tissue contains numerous tumor-associated macrophages, and substantial work has demonstrated significant pathological role for adult glioma-associated macrophages. However, over past decade highlighted many molecular genomic differences between pediatric high-grade gliomas. Thus, we directly compared inflammatory characteristics glioblastoma (GBM). found leukocyte (CD45+) compartment in samples predominantly composed CD11b + macrophages, very few CD3+ T-lymphocytes. In contrast, T-lymphocytes are more abundant GBM samples. RNA sequencing macrophages isolated from tumor revealed DIPG- GBM-associated both express gene programs related to ECM remodeling angiogenesis, but DIPG-associated substantially fewer factors than their counterparts. Examining secretome cells, patient-derived cell cultures secrete markedly cytokines chemokines cultures. Concordantly, bulk single-cell data indicates low absent expression DIPG. Together, these observations suggest milieu microenvironment fundamentally different GBM. The signature cells may contribute lack lymphocytes non-inflammatory phenotype microglia/macrophages. Understanding subtype-specific inform design application immunotherapy-based treatments.